TW467917B - 1-thiogalactose derivatives - Google Patents

Abstract

Disclosed are novel 1-thiogalactose derivatives which inhibit binding of toxins, such as heat-labile enterotoxin or cholera toxin, to their receptors either in vitro or in vivo. Additionally, disclosed are compounds which inhibit binding of organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors.

Description

Printed by the Consumer Cooperatives of the Central Bureau of Accreditation of the Ministry of Economic Affairs 4 6 7 9 17 A7 B7 V. Description of the Invention (1) * Cross Reference to Related Applications This case is US Patent No. 08/75 1,5 1 0, published on On November 15, 1996, a partial sequel, this case affirmed the benefits of the US Provisional Case 1 ^ 60/0 30,794, which was announced on November 14, 1996. The case has been incorporated by reference in its entirety. BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to novel 1-thiogalactose derivatives that inhibit the binding of toxins such as heat-labile enterotoxin (LT) or cholera toxin (CT) to their receptors in vitro or in vivo. . In addition, the compounds of the present invention can inhibit the binding of the enterotoxin-producing strains of organisms (such as bacteria, viruses, bacillus, etc.) such as Vibrio cholerae and Escherichia coli to their cell surface receptors. References The following publications, patents and patent cases are shown with footnotes in this case: 1 Spangler, BD, " Structure and Function of Cholera Toxin and Related Escherichia coli Heat-Labile Hnterotoxin ", Microbiological Reviews, 56⑷: 622-647 (1992) . 2 Hoi, WGJ, et al., &Quot; Structure and Function of E. coli Heat-Labile Enterotoxin and Cholera Toxin B Pentamer ", Bacterial Toxins and i / i Ed. By J. Moss et al., Marcel Dekker,

Inc. (1995). 3 Williams (ed.), Synthesis of Optically Active a-Amino Acids, Pergamon Press (1989). 4 Evans et al., J. Amer. Chem. Soc, 112: 4011-4030 (1990 ). 5 Pu et al., J. Amer. Chem. Soc., 56: 1280-1283 (1991). This paper size is applicable to China Standards (CNS) A4 (2! 0X297 public ^) (Please first (Read the note on the back! Please fill in this page before the matter)

1T printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs a S 7 9 1 7 A7 B7 V. Invention Description (2) 6 Williams et al., J. Amer. Chem. Soc, 113: 9276-9286 ( 1991). 7 Kagen et al., Synlett, 1990, 643-650. ® US Patent No. 5,580,858, issued December 3, 1996, to RM Ippolito et al. 9 M. Dubois et al., Z / ifl / · Diem ., 28, (1979) 350-356. 10 US Patent No. 4,137,401, issued January 30, 1979, to R.

Lemieux et aJ. 11 Η. H. Westal et al.f " Methods of Enzymology, " 34 (b), 64 (1974). 12 T. Mukaiyama et al., Tetrahedron Letters, 56, 5907-5908 (1968 ). 13 Svennerholm, AM. Et al., Current Microbiology, 1: 19-23 (1978). All the above publications, patents and patent cases are incorporated herein by reference in their entirety, and their degree of inclusion is as individual publications, patents or patents Cases are specific and individually incorporated for reference. Technical Statement Toxins produced by organisms such as bacteria, viruses, protozoa, bacillus and other organisms are known to cause many animal and human diseases, including many chancre diseases. For example, heat-labile enterotoxin ("LT"), secreted by an enterotoxin-producing strain of Escherichia coli, has been identified as one of the causes of traveler diarrhea 1 caused by bacteria. In addition, the cholera toxin ("C T") produced by Vibrio cholerae has been identified as the cause of severe chin disease, cholera 1. Known heat-unstable enterotoxin and cholera toxin can be used on the host cell -5- This paper size applies Chinese National Standard (CNS) A4 specification (210X2? 7 mm) (Please read the precautions on the back before filling (This page), -50 4 6 7 91 7 A7 ________B7 V. Description of the invention (3) The oligosaccharide receptor binding is the first step in the pathological development of related disease conditions2. In particular, it is known that LT and CT can be combined with gangliolipid Gmi, which is a type of sugar GMi located on the outer leaflet of the host cell membrane, which has a typical pentasaccharide structure, namely Gal (pi- > 3) GalNAc ( pl- > 4) {NeuAc (a2-3)} Gal (pl ~ ^ 4) Glc 'on its surface can be used as a receptor for LT and CT. LT is also known to bind to other ganglion lipids, such as gangliolipids G D, b. In addition, many toxic organisms (such as bacteria, viruses, bacillus, etc.), including enterotoxic organisms, can bind to cell surface receptors as part of the disease course. For example, bacteria such as Vibrio cholerae and Enterotoxin producing strains of Escherichia coli can directly bind to cell surface receptors to form colonies on adhesion points. This binding is harmful because it interacts with the cell surface to express toxins immediately. In order to soothe or prevent the toxic or harmful effects caused by toxins and organisms, it is highly desired to inhibit the binding of toxins or organisms and their equivalent cell surface receptors. The present invention proposes a novel thiogalactose derivative, which can effectively Inhibit this binding. Key points of the invention Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economics This invention is related to the discovery of a new class of thiogalactose derivatives that can inhibit toxins such as heat labile enterotoxin (LT) or cholera toxin (CT) and their receptors Of combination. The compounds of the invention can also inhibit the binding of organisms such as Vibrio cholerae and Escherichia coli to enterotoxin-producing strains and their cell surface receptors. Therefore, in one of its composition aspects, the present invention proposes a compound of formula I: -6- This paper size is applicable to China National Standard (CNS) A4 specifications. (2Ϊ〇 × 297 公 #> ^ 6 7 91 A7 B7 V. Description of the invention (

Economic and Central Bureau of Standards, Consumers and Consumers Co., Ltd. R1 R1 is selected from the following including hydrogen, alkyl, substituted alkyl, alkenyl, alkylaryl, alkoxyalkyl, aryl, cycloalkyl, cycloalkenyl, Heteroaryl, heterocyclic and thioalkoxyalkyl; R2 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl, cycloalkene R3, heteroaryl, heterocyclic and thioalkoxyalkyl; R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl , Cycloalkenyl, heteroaryl, heterocyclic and thioalkoxyalkyl; or R1 and R2, or R1 and R3, or R2 and R3, or R1, R2, and R3 can be combined with R1 and / or R2 and / or R3 The attached carbon atoms are connected to form a cycloalkyl, cycloalkenyl or heterocyclic ring; H4 is selected from the following including -XR5, -XC (W) R6, -XC (W) X, R7, and -C (W) XR8; Where W is selected from the following including oxygen, sulfur, and NH; and X and; T is independently selected from NR9 including oxygen-sulfur, wherein R9 is selected from hydrogen and alkyl; or when R4 is -XR5 and R5 is not hydrogen, X may also be selected from the following including S (0) · and -S〇2 R5 is selected from the following including hydrogen, alkyl, alkenyl, alkaryl, alkoxyalkyl, _aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic, and thioalkane逋 Chinese National Standard (CNS) A4 broadcast (2 丨 〇 X 297g t) (¾Please read the note on the back before filling in this page}

Η β w Printed by Zhengong Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs d 6 7 9 彳 7, 1 'A7 ____B7 V. Description of the invention (5) group, and when X is -NR9-, then R9 plus X can form an amine Basic acid; or 5 and R1, or R5 and R2, or R5 and R3 can be added to the XR5 group of X and Ri and / or R2 and / or R3 carbon atoms attached to form a heterocyclic ring; R6 is selected from the following including alkane Group, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic and thioalkoxyalkyl; or R ^ kRl, or R6 and R2, or r6 & r3 may be added with xc (w) r6i -XC (W)-moiety and carbon atoms of R1 and / or R2 and / or R3 to form a heterocyclic ring; R7 is selected from the following including aryl, alkenyl, and aryl, Oxygen radical, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic and thioalkoxyalkyl; or R7 and R1, or R7 and R2, or R7 and R3 can be added with -XC (W ) The -XC (W) X,-part of XfR6 and the carbon atoms attached to R1 and / or R2 and / or R3 form a heterocycle; R8 is selected from the following including alkyl, alkenyl, alkaryl, alkoxy Alkyl, aryl, cycloalkyl, cyclofluorenyl, heteroaryl, heterocyclic and thioalkoxyalkyl; or R8 and R1, or R8 and R2, R8 and R3 can be added with the -C (W) X- moiety of the -C (W) XR8 group and the carbon atom attached to R1, R2 and / or R3 to form a heterocyclic ring; Y is selected from the following including sulfur,- S (0)-and -S (0) 2-;

Ra, Rb, R ° and Rd are each independently selected from the group consisting of hydrogen; sulfate; -C (0) R1 (), where R1Q is selected from the group consisting of alkyl, alkenyl, alkaryl, alkoxyalkyl, aromatic , Cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic, and thioalkoxyalkyl; and -P (0) (0R ") 2, wherein each R11 is independently selected from the group consisting of hydrogen, pit, and alkenyl , Burned aryl, oxalyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic and thioalkoxyalkyl: -8-^ Paper size applies to Chinese national standards (CNS > A4 specifications (210X297mm) '~-' (Please read the precautions on the back before filling this page) ir

JT #-4β? 9ι7 Α7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ____. _B7 V. Description of the Invention (6) η is an integer equivalent to 0 or 1; and a pharmaceutically acceptable salt thereof; When R1 and R2 plus carbon atoms attached to R1, R2 & R3 can form a cyclopentyl ring, R3 is hydrogen, R4 is -XR5, χ is oxygen, γ is sulfur, Ra'R'R and R are hydrogen , And 3! Is 1, then non-hydrogen. In a preferred embodiment, the invention relates to isomers of compounds of formula I. In another preferred embodiment, the present invention relates to the β-isomer of the compound: Preferably, R1, R2, R3, R5, R6, RW are selected in the above formula τ so as to form at least one carbocyclic ring (i.e., cycloalkyl or cycloalkenyl) or heterocyclic ring. Preferably, R1, R2, R3, R5, R6, R7 & R8 are selected so as to form two ring completions or heterocycles. In the above formula I, when η is 0, R1 and R2 are well connected, and the carbon to which they are attached forms a ring group with 5 to 7 carbon atoms, and if necessary, it is 3 to 3 groups. To replace. Preferably, R1 and R2, together with the carbon to which they are attached, form a cyclopentane or cyclohexane ring. Dome η is 1, R1 and R2 are preferably connected, and the carbon atoms attached to R1, R2 and r3 are added to form a cycloalkyl group having 5 to 7 carbon atoms, and if necessary, 1 to 3 alkyl groups To replace. Preferably, R1 and R2 are connected, and carbon atoms attached to Ri, r2 and R3 are added to form a cyclopentane, dimethylcyclopentane, cyclohexane, dimethylcyclohexane or cycloheptane ring. In addition, R2 and R3 are preferably connected, and the carbon atom to which they are attached forms an n-pinene ring (ie, a bicyclic [2,2,1] heptagon ring). When R3 is not connected to R2 to form a cycloalkyl ring, R3 is preferably hydrogen. Better R4 basis, examples include: XR5 with specific, X and -9- (Please read the note on the back 1! # 'Fill this page j Order I.. I foot f This paper size applies to China National Standard (CNS) A4 Regulations (2 丨 OX 297g) A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 9 V. Description of the Invention (7) R5 forms an amine, hydroxyl or amino acid , Selected from the group consisting of glycine, .beta-alanine, leucine, histidine, tryptophan, and arginine; or those having the formula -XR5, where X is -NΗ- and R5 is an alkane Or formula -XR5 where X is -N-- and R5 is cycloalkyl; or formula -XC (0) R6 where X is -NH- and R6 is methyl or 2-carboxyphenyl When R4 is -XR5 where X is -NH- and R5 is an alkyl group, the alkyl group is preferably methyl, isopropyl, n-propyl 'second butyl, pent-3-yl, or n-hexyl. In addition, when R4 is _XR5 where X is -NH- and R5 is a cycloalkyl group, the cycloalkyl group is preferably cyclobutyl'dimethylcyclobutyl, cyclopentyl, methylcyclopentyl, dimethyl Cyclopentyl, cyclohexyl, methylcyclohexyl or dimethylcyclohexyl. Ran, Re, Rb, R, and Rd each Independently selected from the following include: hydrogen and -C (〇) R 1 0, wherein R 1 〇 is an alkyl group. Preferably, R a, R b, R c, and R d are each hydrogen. The features proposed by the present invention Examples of the preferred compounds are as follows: 2-Hydroxycyclopentyl_1-ylgalactopyranosyl 2-Hydroxycyclohexyl [-yl 1_thio_0_〇-11 1-phenylbutane_1_yl 1_thiopyran galactose lane (3-hydroxy-n-fluoren-2-yl) methyl 1 · thio_β · 〇 · galactopyranophene 3 plant Jing 5 -1 _ radical 1 _ sulfur _ β · d-ρ galactolane lane 3-cyclamyl_1-yl galactopyranosyl-2, 2-monomethyl_ 4- cyclamyl-1- 1_Sulfur_6 Wind P " D-ρ Biranfeng j 丨 a 4_Epiyl-2-yl 1-thio-β- Dp galactopyranosyl 2, 2-dimethyl_ 5 -# 至 基 cyclohexan-1-radical 1 -sulfur_β 3-kisylcyclohexyl-Kibusulfur _p_D_ ton galactofuran ^ & galactose deficient 10- This paper size applies Chinese national standards (CNS) A4 specification (21 × 297 mm1: Precautions on the back of all readers, please fill out this page)

4 6 7 9 17 A7 B7 Printed by the Central Standard of the Ministry of Economic Affairs 扃 贝 工 consuming cooperatives V. Description of the invention (8) 4,4-Dimethyl-3-hydroxycyclohex-1-yl '蚬 -β_〇_py Galactopyranosyl 2-Aminocyclopent-1-yl1-thio-β-Dp galactose ^: 2-aminocyclohex-1-yl 1-thio-β_0-ρ galactopyranosyl 3 -Amino-1-phenylbut-1-yl 1-sulfur 1_: 0_galactopyranosyl (3-amino n-fluoren-2-yl) methyl 1 · thio_p_D_galactopyranoside 3-Aminocyclohept-1-yl-1.sulfur-β-Dp galactopyranosyl: 2,2-dimethyl-4-aminocyclopentane-eran galactose lane 3 -aminocyclopentane- 1 · yl thio-β-Dv galactopyranosyl: y: 4-aminopentan-2-yl 1-thio-β-Dp galactose 3 · aminocyclohexyl-1 yl -Sulfur β · D-p galactopyranosyl 3-amino-4,4-dimethylcyclohexyl-!-Yl m_D · galactopyranosyl 2-acetamidocyclopentan-1-yl 1- Sulfur-β- £) -ρ galactopyranosyl 2-acetoaminocyclohex-1-yl 1-thio-β-D-galactopyranosyl 3-ethyl ethylamino-1-phenylbutyl- 1-yl 1-thio_p_D_galactopyranosyl 3-3-ethylamine aminoheptan-1-yl I "thio-β-Dp galactophan 3 -ethanylcyclopent-1-yl 1· _β-〇-galactopyranosyl 4-Ethylaminopentan-2-yl 1-thio-p-Dp galactose # 3 -Ethylaminocyclohexyl 1-thiogalactopyranoside ^: 3-Ethylamino-4,4-dimethylcyclohexyl 1-thio_p_D · galactopyranosyl 2- (2-carboxymethylamino) cyclopent-1-yl-1-thiopyran 2- (2-carboxybenzylamino) cyclohex-1-yl1-thio-p_D_galactopyranosyl 3- (2-carboxyamidoamino) -1-phenylbut-1- Gluconosylgalactopyranosyl [3- (carboxybenzylamido) n-fluoren-2-yl] methyl 1-sulfur_0_; 〇_tonalan -11 MM scale is within the Chinese National Standard (CNS) A4 size (210X25 »7mm)

(Please read the notes on the back I fill in t: r this page; I order _ 4 6 7 9 1 7 A7 B7 Printed by the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China—Industrial and Consumer Cooperatives) 5. Explanation of the invention (9 3- ( 2-Aminomethylamino) cycloheptyl + glyphosate ^ anylgalactosyl 3- (2-carboxy "amino" pentan-2-yl group! · Thiogalactopyranosyl 5: (2_ sign Glycine amino) -2,2-dimethylcyclohexyl m_p_D_ galactopyranosyl 3- (2-carboxymethylamino) cyclohexyl] a _thio_Bu D_galactopyranoside Nα- [2- (1-thio-β-D-galactopyranosyl) cyclopentyl]] glycine Nα- [2- (1-thio-β-D-galactopyranosyl) cyclohexyl] yl ] Glycine Nα · [4-phenyl-4- (lHD "pyranosyl) butanyl] glycinate Nα- [3- (〇-thio-β-D · galactopyranosyl ) Methyl) n-single_2yl] glycine Nα- [3- (1 · thio-PD-galactopyranosyl) cycloheptyl] glycine 1 ^ 〇1- [3_ (1_thio -〇14-galactopyranosyl) cycloheptylyl] glycine acid glycine ^ '-monomethyl monothiosulfanyl ^ galactopyranosyl cyclopent-1-yl] glycine Nα- [ 3- (1 · thio-pD-galactopyranosyl) cyclopentyl group] glycine Nα- [4- (1-thio-β-D-galactopyranosyl) ) Pentyl-2-yl] glycine Nα- [4,4-monomethyl-3- (fluorene_thio_p_D_galactopyranosyl) cyclohex-1-yl] glycine Nα- [3 -(1-thio-β-D-galactopyranosyl) cyclohexyl] glycine Nα- [5- (1-thio-β-D-galactopyranosyl) _2,2_dimethyl ring Hex-1-yl] glycine Nβ- [2- (1-thio-β-D-galactopyranosyl) cyclopentyl] _ρ_alanine-12 ^ Paper size applies Chinese National Standard (CNS) Α4 Regulations (210 × 297 mm) (Please read the notes on the back before filling in this page j

A7 B7 467 9 1 V. Description of the invention (10 Νβ- [2- (1-thio-PD-galactopyranosyl) cyclohexyl] _p alanine Nβ_ [4-phenyl-4- (1-thio_β_Β -Galactopyranosyl) but-2-yl] -β-alanine N (3- [3- (〇-thio-PD-galactopyranosyl) methyl) n-fluorenyl-2-]-β-propylamine Acid Nβ- [3- (1-thio-PD · galactopyranosyl) cycloheptylyl] _ρ alanine Nρ- [4,4_dimethyl " 3-G • sulfur β-ϋ-pyridine Galactosyl) cyclopent-1-yl] -β-alanine NP- [3- (1-thio-PD-galactopyranosyl) cyclopentyl] ρ alanine Nβ- [4- (1- Sulfur-β-D-galactopyranosyl) pentyl-2-yl] ρ alanine Nβ- [4,4-dimethylpyranosyl) cyclohex-1-yl] -β-alanine Nβ- [3 · (1-thio-β-D-galactopyranosyl) cyclohexyl βρalanine Nβ- [5- (1-thio-β-D-galactopyranosyl) _2,2_dimethyl Cyclohex-1-yl] -P-alanine Nα- [2- (1-thio-β-D-galactopyranosyl) cyclopentyl] _L_leucine Nα · [2_ (Buthio- β-D-galactopyranosyl) cyclohexyl]] _ L_leucine acid, printed by 〇1- [4-phenyl-4- (1-thio_ | 3_1) _Galactopyranosyl) butan-2-yl ] -L-leucine Nα- [1- (1-thio-β-D-galactopyranosyl) cycloheptan-3-yl] _L_leucine Nα- [4,4-dimethylpyridine Galactosyl) cyclopentan-1 -yl] -L-leucine Nα- [3 · ((fluorene-sulfur-p_D_p) galactopyranosyl) cyclopentyl] _L_leucine Nα- [4- ( 1-sulfur-β-D-galactopyranosyl) pent-2-yl] -L-leucine _____- 13- This paper scale Gujiao — Jia Zhuan (CNS — (21Qx297) ~ " A7 B7 Printed by the Central Laboratories of the Ministry of Economic Affairs, Zhengong Consumer Cooperative, 5 ', Invention Description (11) Να- [4,4-dimethyl-3- (1-thio-β-D-galactopyranosyl) ring Hex-1-yl] leucine Nα- [3-U · sulfur-β-D-galactopyranosyl) cyclohexyl-l-yl] _L_leucine N〇t- [2- (l- Sulfur-β-D-galactopyranosyl) cyclopent-1-ylb L-histidine Na- [2_ (1-thio-β-D-galactopyranosyl) cyclohexyl-i_yl] _L_histidine Nα- [4-phenyl-4- (1-thio-β-D-galactopyranosyl) but-2-yl] -L _histidine Na [3- (l-sulfur -PD-galactopyranosyl) cycloheptan-l-yl-L-histidine Nα- [4,4-difluorenyl-3- (1-thio-pD-galactopyranosyl) cyclopenta- 1-yl] -L-histidine Not- [3- (1-thio-β-D-galactopyranosyl) cyclopent-1-yl l-histidine $ α- [4 · (1 " sulfur-β-Dp galactopyranosyl) pent-2-yl]-+ L-histidine N ex · [4,4-dimethyl- 3-(1-thio-β-D-galactopyranosyl) cyclohexyl-l-yl] -L-histidine Nα- [3- (1-thio-β-D-galactopyranosyl) Cyclohex-1-yl] _L-histidine Not- [2- (1-thio-β-D-galactopyranosyl) cyclopent-1-yl] _L-tryptophanate Na- [2- ( l-thio-β-D-galactopyranosyl) cyclohexyl _; [_ yl;] _ L-tryptophanic acid Not- [4-phenyl-4 · (1-thio-β-D-pyridine Galactosyl) but-2-yl] -L-tryptophan Nα- [3- (1-thio_β_0-galactopyranosyl) cycloheptyl] _L_tryptophan Na- [4,4 -Monomethyl-3- (1-thio-β-Dp than 11 southern galactosyl) cyclopentyl] -L_tryptophan acid \ 〇 ^-[3- (1-thio_ | 3_〇_ Galactopyranosyl) cyclopentyl_1_yl] _1 ^ tryptophan 1 ^ ° ^ [4- (1-sulfur_ | 3 _]:) _ galactopyranosyl) pentyl_2_kib L • Tryptophan 14-M scale scale applicable to t_ ^ i ^ iTA4 ship (2! GX297 public (please read the precautions on the back before filling out this page)-order β H —-two __ 467917 ----- --- V. Description of the invention (12) A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards and Assistance of the Ministry of Carriage and Economy 1 ^ 〇〇- [4,4- 二3- (1-thio_0_; 〇-galactopyranosyl) cyclohex-1-yl] -L-tryptophan Nα- [3_ (1-thio-β-D-galactopyranosyl) ) Cyclohexyl-L-tryptophan Nα- [2- (l-sulfur-β-; D- (r-galactopyranosyl) cyclopentyl_1-yl] _L Arginine Nα · [2- (1-Sulfur-β-D-galactopyranosyl) cyclohexyl-L-arginine Nα- [4-phenyl-4- (1-thio · β · £) -galactopyranosyl ) Butan-2-yl] -L _arginine Na- [3- (l-sulfur-β-D-galactopyranosyl) cycloheptan_1_ylb L_arginine Na- [4 , 4-monomethyl-3_ (1_ 砚 _β_D_galactopyranosyl) cyclopentyl-1.yl] -L-arginine Nα- [3_ (Buthio-β-D-galactopyranosyl) Yl) cyclopentyl] _l_arginine Ncc- [4- (l-sulfur- | 3-D-galactopyranosyl) pent_2_yl] pyridinate Na- [4,4-di Methyl-3- (1_thio · β_D_galactopyranosyl) cyclohex-1-yl] -L_arginine Not- [3- (l · thio-β-D-galactopyranosyl) ) Cyclohexyl] _L_arginine 2.2-dimethyl · 4- (methylamino) cyclopentyl-galactopyranosylpyrene 2.2-dimethyl-4 · (isopropylamino) cyclopentylbuthionine ^ Galactopyranosyl 2.2-dimethyl_4- (n-propylamino) cyclopentyl- 丨 -yl ^ thio, p_D · galactopyranoside 2.2-di -'(((R) -Second-butylamino) cyclopentylsulfanil-galactopyranoside 2.2-dimethyl_4 _ ((S) _Second-butylamino) cyclopentyl-1_ Base 1 sulfur _p_D_ 15 This paper's it standard is applicable to Chinese National Standards (CNs) A4 specifications (210X297 cm) (Please read the precautions on the back before filling this page) Order I-You r

4 6 7 9 V. Description of the Invention (13 Metagalactopyranosyl 2.2-dimethyl_4- (pent-3-ylamino) cyclopentyl_1_yl1_thio_0_〇-pyran galactoide Glycoside 2,2_monomethyl_4_ (n-hexylamino) cyclofluorene q-yl 1_sulfur_0_1) _1? Galactopyranosyl aluminum 2,2 · dimethyl-4- (cyclobutylamino) cyclopentyl -1-yl 1-thio-β-D-galactopyranoside 2,2_dimethyl_4- (3,3-dimethylcyclobut-h-ylamino) cyclopentyl;!-Yl ί -thio-β-D-galactopyranoside 2,2_dimethyl_4- (cyclopentylamino) cyclopent-1-yl 1-thio-β-Dp galactoside 2.2- di Methyl_4- (3-methylcyclopent_1_1ylamino) cyclopent-1_yl 1_thio-β-D-galactopyranoside 2,2_dimethyl_4- (3 , 3-dimethylcyclopentylamino) cyclopentyl-fluorenyl- 1-thio-β-D-galactopyranosyl, alfalfa 2,2-difluorenyl_4- (cyclohexylamino) cyclopentyl_ 1-yl 1_thio_ (3_1) _galactopyranoside 2.2-dimethyl-4- (3-methylcyclohex-1-ylamino) cyclopentyl 1-yl 1-thio-β- D-galactopyranosyl 2,2-diamidyl · 4 · (4-methylcyclohex-1-ylamino) cyclopent-1-yl 1-thio-P-D_galactopyranosyl Rhenium and its pharmaceutically acceptable salts. In another aspect of its composition, the invention proposes A compound of formula I, wherein the compound of formula I can inhibit toxins, preferably heat-labile enterotoxin or Huo 16 Paper ruler (please read the precautions on the back before filling this page) Set the central standard of the Ministry of Economic Affairs A7 B7 4 6 7 9 l 7 printed by the local shellfish cooperative. V. Description of the invention (14) The toxin, which binds to its receptor, or the compound can inhibit the organism's binding to cell surface receptors. Also in its composition In another aspect, the present invention provides a pharmaceutical composition comprising 1-99 wt% of a pharmaceutically acceptable carrier, and 1-99 wt% of at least one compound of the above formula I. In its method aspect, the present invention relates to soothing animals and toxins and their Method for Receptor Binding-Related Conditions' This method comprises administering to the animal an effective dose of a pharmaceutical composition comprising 1-99 wt% of a pharmaceutically acceptable carrier and 1-99 wt% of at least one compound of formula I above, wherein Compounds of formula I can inhibit the binding of a toxin to its receptor. In a preferred embodiment of the invention, the toxin in the previous method is a heat-labile enterotoxin or cholera toxin. In another method of the invention In the aspect, the present invention relates to the state of soothing the binding between animals and organisms and their cell surface receptors. The method includes administering to the animal an effective dose of a pharmaceutical composition containing hMwt% of a pharmaceutically acceptable carrier and 1-99wt. % Of at least one compound of formula I above, wherein the compound of formula I inhibits the binding of an organism to its cell surface receptor. In a preferred embodiment of the present invention, the organism in the above-mentioned method is an enterotoxin-producing strain of Vibrio cholerae or Escherichia coli. The present invention also relates to a carrier containing a 1-thiogalactose derivative, which can be used to inhibit the binding of a toxin to its receptor. Vectors have also been proposed that can be used to inhibit the binding of an organism to its cell surface receptors. Therefore, in another aspect of its composition, the present invention proposes a carrier containing a 1-galactose derivative, which includes a number of covalently bound at least: species 17- sheet paper size_ quiet financial transfer (CNS) test (21 () 297 public interest (please read the notes on the back before filling in this page), ιτο Printed by the Central Laboratories and Consumer Cooperatives of the Ministry of Economic Affairs and printed by the Shell Standard Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy 4 6 7 9 -j η _ / V. Description of the invention (15) a carrier of a compound of formula Γ,

Where R1 is selected from the group consisting of hydrogen, alkyl, substituted pentyl, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic, thioalkoxy Alkyl and linking arms that can covalently link compounds of formula and carrier; R2 is selected from the following including hydrogen, alkyl, substituted alkyl, alkenyl, alkaryl, alkoxy, aryl, ring R3, cycloalkenyl, heteroaryl, heterocyclic, thioalkoxyalkyl, and linker that can covalently link the compound of formula factory to the carrier; R3 is selected from the following including hydrogen, alkyl, substituted alkane Group, fluorenyl group, alkylaryl group, alkoxy group, aryl group, cyclic group, cycloalkenyl group, heteroaryl group, heterocyclic ring, thioalkyl group, and the compound of formula Γ and the carrier can be covalently linked Connecting arms; or Ri and R2, or R1 and R3, or R1, and feet 2 and 3 can be connected to 'plus carbon atoms attached to R1 and / or R2 and / or R3 to form a cycloalkyl, cycloalkenyl Or heterocycle; R4 is selected from the group consisting of -XR5, -XC (W) R6, _xC (W) x, R7, and -C (W) XR8; wherein W is selected from the group consisting of oxygen, sulfur, and nh; and X and- 18- This paper size applies Chinese National Standard (CMS) A4 specification (210X297 Gongchu (I read the precautions on the back before filling in this page)

A7 B7 Printed by the Consumer Cooperatives of the Central Rubbing Bureau of the Ministry of Liji 4 6 7 9 1 V. Description of the invention (te) X 'are each independently selected from the following including oxygen, sulfur and -NR9, where R9 is selected from the following packages_ hydrogen and Alkyl; or when R4 is -XR5, and R5 is not hydrogen, X may also be selected from the following including -S (0)-and -S 0 2-; R5 is selected from the following including hydrogen, alkyl, alkenyl, and alkaryl Group, alkoxyalkyl group, aryl group, cycloalkyl group, cycloalkenyl group, heteroaryl group, heterocyclic ring, thioalkoxyalkyl group, and a linking arm capable of covalently linking a compound of formula IM to a carrier, and When 乂 is _NR9-, then R9 plus X can form amino acids; or R5 and Ri, or and R2, or R5 and R3 can be connected, plus X and R1 and / or and / or R3 of -XR5 group The attached carbon atom forms a heterocyclic ring; R6 is selected from the following including alkyl, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl, cyclofluorenyl, heteroaryl, heterocyclic, sulfur Oxygen radicals and linking arms that can covalently link compounds of formula Γ to the carrier; or R6 and R1, or R6 and R2, or R6 and R3 can be connected, plus -xc (-XC (W) R6 radical) W)-part, and the carbon atom to which R1 and / or R2 and / or R3 are attached forms a heterocyclic ring; R7 is selected from Columns include alkynyl, alkynyl, aryl, alkynyl, aryl, cyclic alkynyl, cycloallyl, heteroaryl, heterocyclic, thiopentyl, and covalent compounds of formula Γ The connecting arm to the carrier; or R7 and R1, or R7 and R2, or R7 and R3 can be connected, plus -XC (W) X, the -XC (w) X,-part of the R7 base, and R1 and And / or R2 and / or R3 carbon atoms form a heterocyclic ring; si8 is selected from the group consisting of pit, fluorenyl, aryl, alkynyl, aryl, cyclopentyl, cyclohomyl, heteroaryl, hetero Ring, succinyl group, and linking arm that can covalently link the compound of formula Γ to the carrier; or R8 and Ri, or ruler 8 and R2, or R8 and R3 can be connected, plus -C (W) XR8 The -C (w) x · part of the base, and the carbon atoms attached to R1, R2 and / or R3 form a heterocyclic ring; -19- This paper size applies Chinese national standard {CNS) A4 specification (210X297 mm >(# 先 闻 读 Note $ item on the back-S-Fill in the purchase)

mJ ·

467917 A7 Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs ______________ B7 V. Issued (17): Y is selected from the following including: sulfur '-S (〇)-and _s (〇) 2 · ;, Rb Re & Rd are each independently selected from the group including hydrogen; sulfate; -0 (0) 111 0 'wherein R10 is selected from the group including alkyl, alkenyl, alkaryl, alkoxyalkyl, aryl, cycloalkyl , Cycloalkenyl, heteroaryl, heterocyclic and thioalkoxy; and 4 (0) (01 (^) 2, where each R " is independently selected from the group consisting of hydrogen, alkyl, alkenyl, and alkyl Group, alkoxyalkyl group, aryl group, cycloalkyl group, cycloalkenyl group, heteroaryl group, heterocyclic ring and thioalkoxyalkyl group; and a linking arm capable of covalently linking a compound of formula factory to a carrier; and 11 Is an integer equivalent to 0 or 1; and a pharmaceutically acceptable salt thereof; the limitation is that R1 ,, 玟 3, r5_, r «5 ,, Rb'Re & Rd is only one of which is connected to the carrier; and further restrictions Provided that when R1 and R2 are connected, the carbon atom attached to R1, R2 & R3 can form a cyclopentyl ring, R3 is hydrogen, X is oxygen, Y is sulfur, and η is 1, then Ra, Rb, RC, Rd & R5 is neither hydrogen nor possibile Covalently linking a linking arm of a compound of formula Γ to a carrier. In another aspect of its composition, the present invention proposes a carrier containing a dithiogalactose derivative, which includes a carrier on which a plurality of at least one compound is covalently bonded. Wherein the compound of the formula Γ can inhibit the binding of toxins to its receptors, or the compound can inhibit the binding of organisms to its cell surface receptors. In terms of its composition, the present invention proposes a pharmaceutical composition containing 1-99 wt% A pharmaceutically acceptable carrier, and a carrier containing 99% by weight of a 1-thiogalactose derivative. In terms of the method, the present invention relates to a method for relieving the condition related to the binding of an animal to a toxin and its binding, and the method includes The animal administers an effective dose of the drug-20- This paper size applies the Chinese National Standard (CNS) A4 Regulation (210X297 mm) (Please read the precautions on the back before filling this page} Order 0, P, ^ 17 9 17 Αν _______B7 V. Description of the invention (18)-a chemical composition containing a pharmaceutically acceptable carrier and a 99% by weight carrier containing a 1-thiogalactose derivative, wherein Formula 1, the compound may be Binding of toxin and its receptor. Θ? In another aspect of the method, the present invention relates to a method for relieving the binding of an animal to an organism and its cell surface receptor, which method comprises administering to the animal an effective dose of a pharmaceutical composition A compound containing 1-99 wt% of a pharmaceutically acceptable carrier and 1-99 wt% of a carrier containing a 1-thiogalactose derivative, wherein the compound of the formula Γ can inhibit the binding of an organism to its cell surface receptor. In the preferred embodiment of the present invention, the carrier used in the above composition and method is a non-absorbable carrier. Preferably, the carrier is a non-absorbable solid phase carrier. Preferred compounds of formula I that can be used in the present invention include the following formula IA: (谙 Please read the note on the back first and then fill in this page) 1 i --Order—

tr Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economics Among them, the choices of R1, R2, R3, R4 and η are shown in Table I below. , -21-This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 467917 A7 B7 V. Description of the invention (19 Table η R1 R2 R3 R4 0 -ch2ch2ch2-…, -ΟΗ 0 -CH2CH2CH2CHr 1- -ΟΗ 1 ~ Φ -CH? -Η -ΟΗ 1 -Η Cyclopentyl-1,3-diyl-〇Η 1 -CH2CH2CH2CHr -Η -ΟΗ 1 -C (CH3) 2CH2- -Η • -ΟΗ 1 -CH2CHr- Η -ΟΗ 1 -CH3 -CHj -Η -ΟΗ 1 -C (CH3) 2CH2CHr -Η -ΟΗ 1 -ch2ch2ch2- -Η -ΟΗ 1 -CH2CH2C (CH3) 2- -Η -ΟΗ 0 -CHjCH ^ CHr-一-νη2 0 -CH2CH2CH2CH2- -νη2 1 -ch3 -Η -νη2 Please read first. Then write down: This page is printed by r Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. -22 This paper applies Chinese national standards ( CNS) A4 size (210 X 297 mm) A7 467917

7 B V. Description of the invention (20) Printed by the Consumer Cooperatives of the Central Commission of the Ministry of Economic Affairs η R1 R2 R3 R4 1 -Η Xuewu-1,3-diyl-nh2 1 -CH2CH2CH2CHr -H -nh2 1 -C (CH3) 2CH2- -H -nh2 1 -ch3 -ch3 -H -nh2 1 -ch2ch2ch2- -H, -NH2 1 -CH2CH2C (CH3) 2- -H -nh2 0 -CH2CH2CHr -NHC (0) CH3 0- CH2CH2CH, CHr -NHC (0) CH3 1 .Φ --ch3 -H .-NHC (0) CH3 1 -H cyclopentane-1,3-tri-NHC (0) CH3 1 -ch2ch2gh2ch2- -H -NHC ( 0) CH3 1 -C (CH3) 2CHr -H -NHC (0) CH3 1 .-ch3 -ch3 -H -NHC (0) CH3 1 -CH2CH2CHr -H -NHC (0) CH3 1 -CH2CH2C (CH3) 2 --H -NHC (0) CH3 0 -ch2ch2ch2- -NHC (0) ^-(2-C00H) 0 -ch2ch2ch2ch2- -NHC (0) < ^-(2-C00H) 1 -ch3 -H -NHC_ -(2_C00H) 1 -H cyclopentyl-1,3-diyl-NHC (O) 0- (2-COOH) 1 -ch2ch2ch2ch2- -H -NHC (O) 0- (2-COOH) 1 -ch3- CHj -H -NHC (O) 0- (2-COOH) 1 -ch2ch2ch2- -H -NHC (O) 0- (2-COOH) 0 -CH2CH2CHr -NHCH2GOOH 0 -ch2ch2ch2ch2- a-NHCH2COOH 1 -Φ -ch3 -H -NHCHjCOOH 1 -H Cyclopentyl-1,3-diyl-NHCH2COOH 1 -ch2ch2ch2ch2- -H -nhch2cooh -23- (Please read the precautions on the back before filling in, write this page) Binding paper Standards apply to China National Standard {CNS) A4 (210X297 mm) 6 4 9 V. Description of invention (21) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs η R1 R2 R3 R4 1 -C (CH3) 2CH2- • H -NHCH2COOH 1 -ch2ch2- -H -nhch2cooh 1 -ch3 -ch3 -H -nhch2cooh 1 -C (CH3) 2CH2CH2- -H -nhch2cooh 1 -ch2ch2ch2- -H -nhch2cooh 1 -CH2CH2C (CH3) r -H- nhch2cooh 0 -CH2CH2CHr a · -nhch2ch2cooh 0 -ch2ch2ch2ch2- — -nhch2ch2cooh 1 -Φ -ch3 -H -nhch2ch2cooh 1 -H penta: 1: 3-diyl '.-NHCH2CH2COOH 1 -ch2ch2ch2ch2ch2- -H C (CH3) 2CHr -H -nhch2ch2cooh 1 -CH2CHr — -H -nhch2ch2cooh 1 -ch3 -ch3 -H -nhch2ch2cooh 1 -C (CH3) 2CH2CH2- -H -nhch2ch3cooh 1 -CH2CH2CHr. -H -nhch2ch2co2co2 CH3) 2- -H -nhch2ch2cooh 0 -ch2ch, ch2- -NHCH (COOH) CH2CH (CH3) 2 0 -CH2CH, CH2CHr -NHCH (COOH) CH, CH (CH3) 2 1 Φ -ch3 -Η -NHCH ( COOH) CH2CH (CH3) 2 1 -ch2ch2ch2ch2- -Η -NHCH (COOH) CH2CH (CH3) 2 1 -C (CH3) 2CH2- -Η -NHCH (COOH) CH2CH (CH3) 2 1. -ch2ch2- -Η -NHCH (COOH) CH2CH (CH3) 2 1 -ch3 -CHj -Η -NHCH (COOH) CH2CH (CH3) 2 1 -C (CH3) 2CH2CHr -Η -NHCH (COOH) CH2CH (CH3) 2 1 -CH2CH2CHr -Η -NHCH (COOH) CH2CH (CH3) 2 0 -ch2ch2ch2- -Η -NHCH (COOH) CHr (imidazole-4 -Base) -24- (Read the precautions on the back before you fill out this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X29? Mm) 4 6 7 9 17 A7

7 B V. Description of the invention (22) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs R1 R2 R3 R4 0 -ch, ch2ch2ch2- -H -NHa ^ COOHKHj-j: imidazole-4-i〇1 -φ -ch3 -H -NHCH (COOH) CH2- (imidazol-4-yl) 1) 1 -ch2ch2ch2ch2- -H -ΝΗ (: ίί ((: ΟΟΗ) (: Η2- (imito-4-yl) 1) 1) 1- C (CH3) 2CHr -H -NHCH (COOH) CHr. (Imidazol-4-yl) 1) 1 -CH2CHr -H -NHCH (COOH) CH2-imidyl's-4-yl) 1) 1 -ch3- ch3 -H -NHCH (COOH) CHr (imid-4-yl) 1) 1 -C (CH3), CH2CH2- -Hf -NHCH (COOH) CH2- (imidazol-4-yl > 1) 1 -ch2ch2ch2 --H -NHCH (COOH) CH2- (imidazol-4-yl) 1) 0 -CH2CH, CHr --- -NHO ^ COOHiCH / pil indole-3-1) 0 -CH2CH, _CH2CHr -NHCH (COOH) CHr (Xindol-3-yl) 1 -Φ -ch3 -H · • NHCH (C〇OH) CH2- (♦ dol · 3-yl) 1 -ch2ch2ch2ch2- -H -NHCH (COOH) CH2- (Xindole: 3-yl) 1 -C (CH3) 2CH3- '-H -NHCH (COOH) CHr (pyridin-3-yl) 1 .-ch2ch2- -H -NHCH (COOH) CH2- (4 indol-3-yl ) 1 -CHj * CHj -H -NHCH (CO〇H) CHr (4 indol-3-yl) 1 -C (CH3) 2CH2CH2- -H -NHCHiCOOHKHrbl indol-3-yl) 1 -ch2ch2ch2- -H -NHCH (COOH) CH2- (y'3-yl) 0 -ch2ch2ch2- — -NHC H (COOH) (CH2) 3NHC (NH) NH2 0 -ch2ch2ch2ch2- -NHCHtCOOHitCH ^ jNHCfNHiNHi 1 • Φ -ch3 -H -NHCH (COOH) (CH2) 3NHC (NH) NH2 1 -ch2ch2ch2ch2- -H -NHCHiCOOHifCH ^ jKHCi ^ 1 -C (CH3) 2CHr -H -NHCHiCOOHKCH ^ jNHCiNHJNHj 1 -ch2ch2- -H -NHCH (COOH) (CH ^ 3NHC (NH) NH2 1 -ch3 -ch3 -H -NHCHfCOOHJiCH ^ sNHCfNH) ^ 1 -C ( CH3) 2CH2CH2- -H -NHCHtCOOHifCH ^ NHCCNH) ^ 1 -CH2CH2CHr -H -NHCH (COOH) (CH2) 3NHC (NH) NH2 1 -C (CH3) 2CH2- -H -NH-CHj This paper is suitable for China National Standard (CNS) A4 Regulations (210X297mm) -25-(I read and read the notes on the back-then the matters and then ^: write this page)

3 7

7 B Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention (23) η Rl R2 R3 R4 1 -C (CH3) 2CHr -H -NH-CH (CH3) 2 1 -C (CH3) 2CH2-- H -nh-ch2ch2ch3 1 -C (CH3) 2CH2- -H -NH-CH * (CH3) CH2CH3 Isomer 1 -C (CH3) 2CHr -H -NH-CH * (CH3) CH2CH3 * (s)- Isomer 1 -C (CH3) 2CHr -H -NH-CH (CH2CH3) 2 1 -C (CH3) 2CH2- -H -NH- (CH2) 5CH3 1 -C (CH3) 2CH2- -H -NH- Tomb-1-Tomb: 1 -C (Cfi3) 2CHr -H -NH- (3,3-Difluorenyl) cyclobut-1-yl 1 -C (CH3) 2CH2- -H -NH-Cyclidine- 1-yl1-C (CH3) 2CH2- -H -NH- (3-methyl) cyclopent-1-yl 1 1 -C (CH3) 2CH2- -H -NH- (3,3-dimethyl ) Cyclopent-1-yl 1 -C (CH3) 2CHr -H -NH-cyclohex-1-yl 1 -C (CH3hCHr -H -NH- (3-methyl) cyclohex-1-yl 1 -G (CH3) 2CH2- -H • NH- (4-methyl) cyclohex-1-yl Description of the Drawings Figure 1 illustrates the preferred reaction scheme, which can be derived from (X, β-unsaturated carboxyl compounds, i.e. rings Hept-2-en-1-one is made into a variety of 1-thiogalactose derivatives. Figure 2 illustrates a preferred reaction scheme, which can be prepared from tx-halocarbonyl compounds, that is, 2-aircyclohexanone. Into various 1-thiogalactose derivatives. Description The present invention relates to a compound in a specific example, which can inhibit toxins, such as heat-labile enterotoxin or cholera toxin, and its receptor in a test tube-26- This paper applies Chinese National Standard (CNS) A4 specifications (210X297mm) (谙 Please read the notes on the back before filling this page)

Produced by the Central Bureau of Standards of the Ministry of Economic Affairs for Consumer Cooperation Du printed 4 6 / y 1 7 A7 _ B7 V. Combination within the description of the invention (24) or in the living body. In another specific example, the compounds of the present invention inhibit the binding of organisms (e.g. bacteria, viruses, bacillus, etc.), such as cholera or Escherichia coli enterotoxin-producing strains, to their cell surface receptors. However, before describing the present invention, the following terms are defined. The definition "fluorenyl" refers to alkyl-C (0)-, aryl-C (0)-and heteroaryl · (:( 0)-, wherein alkyl, aryl and heteroaryl are as defined herein. "Amino" refers to -C (0) NRR, where each R is independently hydrogen or alkyl. "Amino" refers to alkyl-c (o) o-, aryl-c (o) o ·, Heteroaryl • c (o) o · and heterocycle-c (0) 0-, where alkyl, aryl, heteroaryl and heterocycle are defined as such. "Alkylaryl" refers to -alkylene- An aryl group preferably has 1 to 8 carbon atoms in the alkylene moiety and 6 to 10 carbon atoms in the aryl moiety. Examples of the alkaryl group include benzyl, phenethyl, and the like. "Alkoxy" refers to Alkyl-0 .. Examples of such alkoxy groups include: methoxy'ethoxy, n-propoxy, isopropoxy, n-butoxy, third-butoxy, second-butoxy Group, n-pentyloxy, n-hexyloxy, i, 2 · dimethylbutoxy, etc. "Carbooxy" refers to a monoalkyl-O-alkyl, examples of which include fluorenylmethyl (ch3och2,) , Ψ oxyethyl (ch3-o-ch2ch2_), etc. "Amidino" means that the amidino has preferably 2 to 8 carbon atoms, and preferably 2 to 6 carbon atoms, and has at least 1 And preferably 1-2 alkenyl unsaturated positions. This alkenyl includes vinyl (-CH = CH2), n-propenyl (ie allyl) (-CH2CH = CH2), iso-propenyl (-C (CH3) = CH2), etc. ___ -27- This paper size applies the Zhongguanjia Standard (CNS) A4 specification (21〇 ×? '' (Please read the cautions on the back before filling in this page)

., 1T printed by the Central Bureau of Standards of the Ministry of Common Cars, printed by the Shellfish Consumer Cooperative, A7 —______________ —__ 5. issued. (25) “Alkyl” refers to a monovalent alkyl group, having 1 to 8 carbon atoms and preferably 1 To 6 carbon atoms. Examples of this term include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-hexyl and others. "Substituted pit group" refers to a branched or straight chain fluorenyl group of 1 to 8 carbon atoms, having 1 to 3 substituents selected from the following including hydroxy, fluorenyl, fluorenylamino, fluorenyloxy, alkoxy , Alkenyl, alkynyl, amine, aminoamino, aryl, aryloxy, carboxyl, carboxyalkyl, cyano, cycloalkyl, guanidyl, haloaryl, heterocyclic, nitro, Thiol, thioaryloxy, thiaaryloxy, etc. Preferred substituents include hydroxy and amine. "Alkylene" or "alkanediyl" refers to a divalent alkylene, preferably having 1 to 8 carbon atoms and more preferably i-6 carbon atoms. Examples of this term include methylene (-CH2-), ethylene (-CH2CH2_), propyl isomers (such as -CH2CH2CH2- and CH (CH3) CH2 ·), and the like. "Alkynyl" means that the bulk preferably has 2-8 carbon atoms and more preferably 2-6 carbon atoms' and has at least 1 and preferably 1-2 alkynyl unsaturation. This alkynyl includes ethynyl (-CsCH), propargyl (CH2C = CH) and the like. "Amino acid" means any naturally occurring amino acid, as well as synthetic analogs and derivatives thereof. The a-amino acid includes a carbon atom in which an amine group, a carboxyl group, a hydrogen atom, and various groups are called "side chains". The naturally occurring side bonds of amino acids are well known in the art, and include, for example, amidine (as in glycine), alkyl (as in alanine, valine, leucine, isoleucine, proline) Acid), substituted alkyls (such as threonine, serine, methionine, 'semi-deamidated', aspartic acid, aspartic acid, aspartic acid, glutamic acid, glutamine, spermine Acid and lysine), alkaryl (such as amphetamine and tryptamine-28-this paper size applies to Chinese National Standard (CNS) A4 specifications (2 丨 0X297 mm) one-(Please read the back (Please fill in this page again)

" m

4 6 7 9ι 7 A7 __B7 printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives V. Description of the Invention (26) acid), substituted aralkyl (such as tyrosine) and heteroarylalkyl (such as in histamine'). Artists should understand that the so-called "amino acids" also include β- 'γ-, δ-, and ω-amino acids. Unnatural amino acids are also known in the art and are shown in, for example, W i 11 iam s3, Ε ν anseta 1. 4, Pueta 1.5 * s Williams et al. 6, all of which are listed here for reference. 20 traditional amino acids, stereoisomers of unnatural amino acids (Such as D-amino acids), such as α, ot-disubstituted amino acids and other non-traditional amino acids are also suitable components in the compounds of the present invention. Examples of non-traditional amino acids include: Aminoproline, 3-methylhistamine, 5-hydroxylysine, and other similar amino acids and imines (eg, 4-hydroxyproline). "Aminomethyl" refers to- NRC (0) R group, where each R is an independent hydrogen or alkyl group "" Aryl "refers to an unsaturated aromatic carbocyclic group having 6-14 carbon atoms, having a single ring (such as phenyl) or Multiple condensed rings (such as naphthyl or anthracenyl) ^ Preferred aryl groups include phenyl, triphenyl, etc. Unless otherwise defined for the aryl substituent, this aryl group may be 1 to 3 selected from the following Substituted by substituents, including: hydroxy, fluorenyl, fluorenyl, alkyl, substituted alkyl, alkoxy, fluorenyl, alkynyl, amino / amido, aryl, aryloxy, carboxyl , Carboxypo, cyano, halo, nitro, heteroaryl, tridentate methyl, etc. Preferred substituents include alkyl, alkoxy, self, carboxy, cyano, nitro, trismethyl , And thioalkoxy. "Aryloxy" refers to an aryl-0- group, where aryl is as defined herein, including optionally substituted aryl groups, and is also defined as such. "Carboxy" refers to- COOH-based. Read A, read, read back · 3 Write: This page is ordered 29- This paper is suitable for the size of the paper • Use the Chinese national standard (CNS > Λ4 size (210X29? Male f) 4 b / 9 1 7 Ministry of Economic Affairs Printed by A7 B7 of the Consumer Standards Cooperative of the Central Bureau of Standards 5. Description of the Invention (27) "Carboxyl" refers to -C (ο) 〇 alkyl, where alkyl is defined as such. "Cycloalkyl" means from 3 to 8 A cyclic alkyl or cyclic alkyl ring of one carbon atom, having a single cyclic ring or multiple condensed rings, which may be 1 to 3, optionally substituted by a substituent selected from the following, including Hydroxy, fluorenyl, fluorenyl, alkyl, substituted alkyl, alkylene, alkoxy, fluorenyl, alkynyl, amine, amine, aryl, aryloxy, carboxyl, carboxyalkane Cyano, cyano, nitro, nitro, heteroaryl, trinanyl, etc. Preferred substituents include alkyl, alkoxy, carboxyl, cyano, nitro, trinanyl, and sulfane Examples of this cycloalkyl group include monocyclic structures such as cyclopropyl, cyclobutyl'cyclopentyl, cyclooctyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2-methyl Cyclo-octyl, etc., or multiple ring structures, such as adamantine and others, and spiro compounds. Examples of suitable cycloalkyl rings include monocyclic structures such as cyclopentane / cyclohexane, cycloheptane, cyclooctane, etc., or multiple ring structures such as bicyclo [2,2,1] heptane, bicyclic [3,2,1] octane, etc. Preferred cycloalkyl rings include cyclopentane, cyclohexane, cycloheptane and bicyclo [3,2,1] octane. "Cycloalkenyl" refers to a cyclic alkenyl or cyclic alkenyl ring of 4 to 8 carbon atoms, having a single cyclic ring, and at least one internal point of unsaturation, which may be 1 to 3 selected as required Substituted by the following substituents, including: via, fluorenyl, fluorenyl, alkyl, substituted alkyl, alkylene, alkoxy, alkenyl, alkynyl, amine, amine fluorenyl , Aryl, aryloxy, a few aryl, a few alkynyl 'cyano' nitro 'heteroaryl, tridentate methyl and the like. Preferred substituents include alkyl, alkoxy, halo, carboxyl, cyano, nitro, trimethylol and thioalkoxy. Examples of suitable cycloalkenyl groups include, for example, cyclobut-2-enyl, cyclopent-3-alkenyl ' cyclooct-3-ol, and the like. This ring is based on examples including ring 30-(read first, read the notes on the back, then fill out this page)

Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 467917 A7----- ___________ B7 V. Explanation of Friends (28) ^ Pentene, cyclohexene, etc. "Halogen" or "halogen" means fluorine, chlorine, bromine and iodine, and is preferably gas or bromine. "Α-South carboxy compound, means a compound having the formula: q_CHr1_ C (0) R2, where ri and R2 are as defined above, and Q is chlorine, bromine, or oxo. This α-Silkyl compound includes by way of example α_Gasaldehyde, α_Bromoaldehyde, α-Baconic acid 'α-Acetonone' α · Bromone, α_Cetone, etc. "Heteroaryl" refers to a monovalent aromatic carbocyclic ring having 2 to 8 carbon atoms Group, having 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur in the ring. Unless otherwise restricted by the definition of a heteroaryl substituent, this heteroaryl group may optionally be 1 to 3 selected from the following Substituted by substituents, including alkyl, substituted alkyl, alkoxy, aryl, aryloxy, south, nitro, heteroaryl, thioalkoxy, thioaryloxy, etc. This heteroaryl The group may have a single ring (such as pyridyl or furyl) or multiple condensed rings (such as daphnyl or benzopyrimyl). ^ Preferred heteroaryl groups include uridine,! Furyl and "Heterocyclic" or "heterocyclic" refers to a monovalent saturated or unsaturated group having a single or multiple condensed rings containing 1 to 8 carbon atoms and 1 to 4 hetero atoms selected from nitrogen, sulfur, or oxygen Atom to ring For the purposes of this case, the so-called "heterocyclic, 'or" heterocyclic "does not include hydrocarbon rings (ie, mono- or oligosaccharides). Unless otherwise restricted by the definition of a heterocyclic substituent, this heterocyclic ring may optionally be 1 Substituted with 3 substituents selected from the group consisting of alkyl, substituted alkyl, alkylene, alkoxy, aryl, aryloxy, nitro, heteroaryl, thioalkoxy , Thioaryloxy, etc. This heteroaryl group may have a single ring (such as pyridyl, hexahydrop-pyridyl, morpholinyl or tetrahydrocranyl) or multiple condensed rings (such as fluorinyl) ). -31-The size of this paper is applicable to the Chinese National Standard (CNS) A4 Specification < mm) (Please read the notes on the back first and then 1 .. the page of this page). Printed by the cooperative 4 6 7 9 1 7 '· A7 B7 V. Description of the invention (29) Examples of nitrogen heterocycles and heteroaryl groups include the following, but are not limited thereto: pyrrole, imidazole, pyrazine, P ratio bite, p ratio Ploughing, pyrimidine, digging, cultivating, 11 different flowers, * 5 Bu Duo, tf 荅 Jun, drinking purine, Ha Ping, Id Chap forest, C Kuifing forest, whistle, auditing I » Ratio , 4 difficult leaching, 4 Jun leaching, Xin leaching, P hysteria, Ye Jun, Ye Lin, Zhong Dian, p'f qi, ># * # ·, Iso Psaijun, Zhong P well, I ton tons, Brown, whistle, brown P Saihu, Mi Jun bite, Mi Tu Lin, hexahydro 0 ratio disease, hexa hydrogen U ratio P well, "5 Budu", etc. "Michael acceptor" refers to the following general formula (I) Of α, β-unsaturated carbonylation .. ...... 0

, II R'-CH = C-C-R2 π R3 where R1, R2 and R3 are defined as such: or RiCHsCR2-C (0) XR8, where R1, R2 'R8 and X are as defined herein. Examples of this Michael acceptor include: α, β unsaturated aldehydes, α, β -unsaturated ketones, α, β -unsaturated esters, α, β -unsaturated thioesters, α, β -unsaturated pyramine #. "Sulfuryloxyalkyl" refers to a nonyl group. * S-methyl group, examples of which include: thiomethoxymethyl (CH3SCH2-), thiomethoxyethyl (Ch3-S.ch2ch2-), and the like. "Thiol" refers to the -SH group " "thioalkoxy" refers to -S-alkyl, where alkyl is as defined herein. "Sulylaryloxy" refers to aryl-S ·, where aryl is as defined herein, including optionally substituted aryl, as such. -32- This paper size applies to China National Standard (CNS) A4 (2IOX297mm) -3 (#Read the precautions on the back before leaving this page)

4 6 7 9] 7 A7 B7 V. Description of the invention (3〇) '"Heteroaryloxy refers to heteroaryl-S-, where heteroaryl is as defined herein' includes substituted heteroaryl as required The radical is also defined in this way. The so-called "chain arm" refers to a chemical group or a covalent bond that covalently attaches a 1-thiogalactose derivative to a carrier as required. This group usually includes an alkylene group and an alkylene group. Or an alkylene aryl group, and at least one heteroatom, preferably 2 to 6 heteroatoms. The particularly preferred link arm is shown in the following formula: (1-thiogalactose derivative) -NH- (CH2) m-NHC (0) NH- (carrier) where m is an integer from 2 to about 10. Preferably, melons are 6. The so-called "carrier" refers to an inert substance or component, which is covalently attached thereto either directly or via a link arm ' 1-thiogalactose derivatives. When used in vivo, the solid-phase carrier must be biocompatible and pharmaceutically acceptable. Preferably, the carrier is a non-absorbable carrier, that is, the carrier may not be used orally The affected area passes through the intestinal tract without being absorbed into the circulatory system, and can be completely completely self-repellently eliminated. Β Better 'carriers are non-absorbable solid phase carriers. Typical and In other words, the carrier may contain many attachment sites for the 1-thiogalactose derivative, that is, the body is preferably an oligo- or polyvalent carrier. Suitable carriers have been described to include low molecules, such as 1, 3 , 5-trimellitic acid (trimellitic acid) to organic and inorganic polymers, polysaccharides, peptides, glass, silicates or minerals. The Central Standards Bureau of the Ministry of Economic Affairs-Industrial and Consumer Cooperatives printed the so-called "solid phase carrier" Refers to an inert, non-absorbable solid substance, in which a 1-thiogalactose derivative is covalently bonded via a link arm β. When used in vivo, the solid phase carrier is biocompatible and pharmaceutically acceptable Examples of suitable solid-phase carriers include sand and gravel, such as synthetic hard acid, such as porous glass; biological silicates, such as diatomaceous earth; hydrogels; silicate-containing minerals, such as Kaolin; synthetic polymers, such as polystyrene, polypropylene _-33-, Zhang scale appropriate • Uses Chinese National Standard (CNS) Α4 specifications (Gong Pan) ----- Offshore Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Yinli 467917 A7 __ B7 V. Description of the invention (31) ene Φ; polysaccharides such as dextrose , Cellulose (CMC), alginate, chitin, chitosan, and cyclodextrin; etc. The preferred solid phase carrier material that can be used in the present invention is a silica carrier, which has been used with omega-amines. Aminoalkyltrialkoxysilanes are aminated with conventional silyl groups. Suitable omega-aminoalkyltrialkoxysilanes include, for example: 3-aminopropyltriethoxysilane, 4-aminobutyltrisilane Ethoxysilane, etc. A particularly good hair stone that can be used in this silyl amination reaction is Manville Corp., Denver, C ο 1 orad 〇. The product name is Chromosorb P τ M dream stone. So-called "toxin" A compound produced by an organism that causes or stimulates the development of toxic, harmful or adverse effects in a host where toxins occur. The adverse conditions include fever, heart palpitations, illness, weightlessness, neurological disorders, renal disorders, bleeding, and the like. As used herein, the so-called "toxins" include bacterial toxins, such as cholera toxin, thermo-labile and thermostable coliform toxins, Clostridium difficile toxins A and B, aerobic lysine, Hemolysin, etc .; toxins produced by protozoa, such as Giardia flagella; toxins produced by Ascaris, etc. Included in this term are exotoxins, that is, toxins secreted by the organism as extracellular products, and enterotoxins, The toxin that appears in the intestine of an organism. The so-called "heat-labile enterotoxin" or "LT" refers to the enterotoxin of the enterotoxin-producing strain of Escherichia coli, which can initiate traveler diarrhea and related conditions. This toxin It has the activity of exogenous lectins. The so-called "traveler's diarrhea" refers to the sudden diarrhea, often accompanied by abdominal colic, vomiting and fever, and occasionally occurs in travelers, often during the first week of the journey . This diarrhea is most often cited by the enterotoxigenic strain of Escherichia coli -34- This paper size is applicable to the national standard of Ningguo (CNS) A4 size (210X297 mm) (#Please read the note on the back before filling in this page)

The Consumer Cooperative of the Central Government Bureau of the Ministry of Economic Affairs of the People's Republic of China printed A7 B7 V. Invention description (32) The so-called "cholera" refers to the acute epidemic infection caused by Vibrio cholerae, among which Vibrio is released in the intestine Soluble toxins can change the permeability of the mucosa, causing significant aqueous diarrhea, large loss of fluids and electrolytes, and dehydration and weakness, but there is no substantial change in the shape of the intestinal mucosa. "Cholera toxin" or "CT" refers to the enterotoxin of Vibrio cholerae, which can initiate cholera and related conditions. This toxin has lectin-like activity. "Inhibiting the binding of a toxin to its receptor, the term means that a compound inhibits the binding of a toxin to its receptor by at least 20%. For example, useful binding inhibition assays can be used to measure gangliosides Goib or gangliosides. The inhibitory effect of boat binding, cytotoxic neutralization, etc. This combination is expressed by the percentage of toxin activity left behind, so that the compound will retain about 80% of the toxin activity under the bioanalytical conditions disclosed herein, indeed Can inhibit the binding of toxins to its receptors. '' "Inhibit the binding of heat-labile enterotoxin (LT) and / or cholera toxin (CT) to LT and / or CT receptors" means that the compound can inhibit ^ And / or the binding of CT to LT and / or CT receptors is at least 20000. "Inhibiting the binding of an organism to its cell surface receptors means that the compound can inhibit organisms, such as bacteria, viruses, protozoa, tadpoles, etc. Binding to its cell surface receptors. For example, an organism such as an enterotoxin producing strain of Vibrio cholerae or Escherichia coli can inhibit the binding of the organism to cell surface receptors. This means that if it can reduce the adhesion of bacterial surface antigens, such as Cfa [the binding of ciliates to at least 10%. The so-called ‘pharmaceutically acceptable salt’ refers to the pharmaceutically acceptable compound of Formula I. 35- This paper size is applicable to Chinese national standards (CNS> A4 specification (2 丨 OX297 mm)

Α7 Β7 Printed by Shelley Consumer Cooperative of Central Standards Bureau of Ministry of Economic Affairs 467917 V. Description of the Invention (33 salt, this salt is derived from organic and inorganic counter ions well-known in various techniques, and examples include sodium, potassium, calcium, magnesium, Ammonium, alkylammonium, etc .; when the molecule contains basic functional groups, it is a salt of organic or inorganic acid, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate; Oxalate, etc. For the purpose of this case, all sugars are listed using the traditional three-word nomenclature as a reference. Unless otherwise indicated, all sugars are D-type, except for fucose, which is L-type. Furthermore, all sugars are pyranose. When the palm center is present in the 1-thiogalactose derivative of the present invention, rather than the palm center of the galactose part, the present invention includes all possible stereoisomeric For example, when η is 0 in Formula I, the carbon atoms to which the ruler 1 and ruler 2 are attached have the R'R or R'S or S'R or S, S configuration. Similarly, when, R, The carbon atoms to which R and R are attached can be ruler, ruler, ruler or 8, ruler, ruler or ruler '8'11 or ^ _' 1? 1'8 8,8,11 or 8,11,8 or 11,8,8 or S, S, S configuration. General synthetic steps The 1-thiogalactose derivative of the present invention can be prepared by the following general methods and steps. It should be understood that When a typical or preferred process (reaction temperature, time, mole ratio of reactants, solvent, pressure, etc.) is shown, other process conditions may be used unless otherwise stated. The optimal reaction conditions may vary with The particular reactant or solvent used will vary, but this condition is determined by the best practice of the skilled artisan. The 1-thiogalactose derivatives of the present invention are usually composed of 2, 3, 4, 6- 0 -Protected 1-thiogalactose intermediate and α, β-unsaturated carbonyl compound or α_ -36-This paper size applies to China National Standard (CNS) A4 specification (210 × 297 mm) I. \. I # First read the Weeping Matters on the back #fill ^ Ben Gong)

i ----— Α. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 7 9 17 _ V. Description of the invention (34) A7 B7 Halocarbonyl compounds are reacted to produce β-containing intermediates containing carbonyl groups which are then reduced or reduced. Sexual amination to form alcohols or amine compounds. If desired, these alcohols or amine compounds can be further derivatized, i.e. reacted with alcohols, alcohols, halates and isocyanates to form esters, amines, carbonates, ureas and the like. Amine compounds can also be reductively alkylated with aldehydes and ketones to form secondary amines. This derivatization of alcohols and amines is well known to those skilled in the art and can be accomplished using established procedures. The α, β · unsaturated carbonyl compound used for preparing the 1-thiogalactose derivative of the present invention has the following formula (II): 〇R ^ CH ^ CC-R2 I R3 Π wherein R1, R2 and R3 are as defined above; Or r ^ CK ^ CR2-C (0) XR8, wherein R1, R2, R8 and X are as defined above. Compounds can be prepared from commercially available materials either commercially available or using procedures well known in the art. For example, this compound can be prepared from aldehydes, RkHO, and β-carbonyl orthophosphate 'such as (Ph) 3PC (R3) C (〇) R2 using the Wittig reaction. Preferred α, β-unsaturated carbonyl compounds for use in the present invention include, by way of example, cyclopenta-2-en-1-one, 4,4-dimethylcyclopent-2-en-1-one , Cyclohex-2-ene-1-rim, 4,4-dimethylcyclohex-2-en-1-one, 6,6-dimethylcyclohex-2-en-1-one, cyclopentyl Ketene and ketone and 2-methylene-2-ketone. 37- The paper size of the table applies the Chinese National Standard (CNS) Α4 regulations (210 × 297 mm (please read the If item on the back before filling in the lettuce page)}

A7 B7 ^ 17 V. Description of the invention (35) The α-self peptidyl compound used to prepare the 1-thiogalactose derivative of the present invention has the following formula: Q-CHRLC ^ C ^ R2, among which ... and! ^ As defined above, and Q is chlorine, bromine or iodine. This compound is commercially available or can be prepared from commercial substances using established procedures. Examples of preferred? -Halocarbonyl compounds which can be used in the present invention include 2-gasocyclone and 2-gasohexanone. Alternatively, a carbonyl compound having a leaving group other than a halogen at the α-position may be used. Suitable leaving groups include various ester groups such as toluate, formate, brosylate and nosylate, etc., as well as fluorinated sulfonate groups, such as trifluorosulfonate, nonafluoro Sulfonate and tr e sy 1 ate groups. Various 1-thiogalactosyl derivatives are synthesized from α, β-unsaturated carbonyl compounds or α-haloquinyl compounds, which are illustrated in Figs. 1 and 2, respectively. Figure 1 illustrates the synthesis of various 1-thiogalactose derivatives from cycloheptan-2-fluoren-1-one. Figure 2 illustrates the synthesis of various 1-thiogalactose from 2-cyclohexanone. Those skilled in the art should easily understand that the synthetic steps described in the reaction conditions shown in Figs. 1 and 2 and below can be changed, and suitable starting materials and reagents can be selected to make other 1-thiogalactose derivatives of the present invention. As shown in Figure 1, D-galactose is fully laurelized, that is, D-galactose is contacted with at least 5 equivalents, and preferably 10 equivalents, of laurel base gas. The reaction is usually carried out in an inert diluent such as pentane, hexane, dichloromethane, etc., and a tertiary amine such as pyridine or triethylamine is used to neutralize the hydrogen gas generated in the reaction. Preferably, a catalyst amount of 4- (N, N-dimethylamino) pyridine is added to the reaction mixture to promote the reaction. Generally, the reaction is carried out at a temperature of from about -7 ° C to about 30 ° C for about 0.5 to about 96 hours to produce -38- The paper bearing standard is applicable to the Chinese Enclosure Standard (CNS) A4 Specifications (210x297 Gongchu) ^ Li-(Please read the precautions for Kenme before & write this page)-Order Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 467917 A7 __B7 V. Description of the invention (36) 1,2,3,4,6-wood-O-laurinyl-〇; -0- | 1 galactopyranosyl, 1, from |) _ Galactose has about 70% The yield. Compound 1 is reconverted to 1-S-ethynyl-2,3,4,6-methyl-0-lauryl-1-thio-β-D-p-galactopyranosyl, 2, ie 1 with excess Thiol-acetic acid reaction. In a specific example, 'this reaction is usually carried out in the presence of an excess of trifluoride butterfly compound, preferably about 15-20 equivalents of boron trifluoride etherate based on 1, in an inert diluent, such as two Methyl chloride and so on. Typically, this reaction is performed initially at about 0eC, then at about 20 ° C to about 30 ° F, for about 0.5 to about 48 hours. In another specific example, compound 2 can be prepared from 1, by contacting 1 with at least one equivalent, preferably 1-1.2 equivalents of benzylamine, to selectively remove the lauryl group. This reaction is usually carried out at about 25 ° C to about 30 X :, is about 96 hours to generate 2,3,4,6 --- 0-lauroyl _ (〇1,0) _pyran hem Lactosides. This intermediate is then converted into 〇_ (2,3,4,6-^-lauroyl) ((α, β) -galactopyranosyl) trichloroacetimidate intermediate, which will soon be laurel The fluorenyl compound is contacted with an excess of trichloroacetonitrile, preferably from about 10 equivalents, and from about 0.8 to about 1.0 equivalents of 18-diazodicyclo [54, 〇] undec-7-ene (DB U), in In an inert diluent, such as methane. The resulting O-dichloroethyl imine acid is then contacted with an excess of thiol acetic acid in an inert diluent, such as dichloromethane, for about 1 to 96 hours at about 25 ° C to about 300 ° C. To produce 1-s-ethenyl-2,3,4,6-cyclo-0-lauryl-1-thio-β-D-galactopyranosyl, 2. In yet another specific example, compound 2 may be composed of compound 1 and about 5 to about 2.0 equivalents of thiol acetic acid and about 0.05 equivalent of trimethylsilyl trifluoromethane

4 6/917 A7 ______ B7 V. Description of the invention (37) ~ The alkane sulfonate (based on 1) is prepared by contacting it in an inert diluent such as digas burner. Typically, this reaction proceeds initially at about 00C, then at 20 eC to about 30 eC, for about 0.5 to about 72 hours. This method is particularly good because it provides the highest yield of Compound 2 and produces comparable measurable α-isomers in traceless amounts. However, when it is desired, the α · isomer, i.e., ethyl-2-, 3,4,6-methyl-0-lauryl-1 -thio-α-D-galactopyranosyl, can be easily Prepared by contacting compound 1 with an excess, preferably about 20 equivalents, of thioacetic acid in the presence of about 1.ο-ΐ. 1 equivalent of tin (IV) chloride, in an inert diluent, such as toluene, at ambient temperature The calendar lasts about 0.5 to about 2 hours. In addition, Compound 1 is treated with an excess, preferably from about 3 to about 6 equivalents of thioacetic acid, and about 20 to 30 equivalents of trimethylsilyl trifluoromethanesulfonate is present in an inert diluent 'Such as dichloromethane, at ambient temperature for about 12 to about 48 hours, can produce 1-S-ethenyl-2,3,4,6. a_D. galanose. The Central Bureau of Standards, Ministry of Economic Affairs, Shellfish Consumer Co-operative Co., Ltd. printed the compound 2 rows of Michael addition to cyclohept-2-ene-1-fluorene, which regenerates cycloheptan-3-yl 2,3,4,6-6--0- Lauryl-1-thio-β-D-p galactopyranosin, 3. This reaction is usually carried out by contacting 2 with at least one equivalent, more than 1.0-1.2 equivalents of cyclohept-2-en-1-one, and the presence of a molar excess of a second terminal amine, such as diethylamine. Without intending to be bound by theory, the salt-based dialkylamine reacts first with the thioethenyl group of compound 2, so that the thiol derivative of compound 2 is formed in situ, and then under the basic conditions produced by dipitamine React with Michael adduct. Typically, this reaction is performed in an inert diluent, such as digas methane. -40- This paper size applies to Chinese national standards (CNS) A4 regulations (2tOX297 mm) 467917 A7 B7 Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Printed 5. Description of the invention (38 Temperature from about -4 ° C to about 50 ° C for about 1 to about 6 hours. The carbonyl group of compound 3 is then reduced with a reducing agent to form 3-hydroxycycloheptyl 2,3 , 4,6 -Mao-〇-Lauryl-1-thio_p_D-n galactose, 4. Better 'This reduction is carried out by contacting 3 with sodium borohydride, preferably about 1_2 To about 2.0 equivalents of sodium borohydride (whichever is 3). Generally speaking, the reaction is performed in an inert diluent, such as tetrahydrofuran, isopropanol and mixtures thereof, and the temperature is from about 2SX: to About 30 ° C, from about 0.5 to about 3.0 hours. The alcohol 4 produced can be easily purified by C18 silica solid phase extraction, and pentane is used as the eluent. The lauryl cracker is removed from the alcohol 4. Use 4 to treat with excess sodium methoxide in methanol and inert diluent, such as digas methane, at about 25 ° C to about 30 ° C for about 1 to about 24 hours. The reaction mixture is neutralized with Ainberlite IR_50S (H +) resin, which can generate 3-hydroxycycloheptyl ^ thio ^ -galactopyranoside, A5. In addition, compound 3 can be reductively aminated to generate 3 aminocycloheptyl 2,3,4,6-6- · lauroyl galactopyranosylamine, 5. In a specific example of the present invention, compound 3 is in excess of ammonium acetate and at least 1 equivalent of sodium cyanoborohydride ( 3) contact. This reaction is usually carried out in an inert diluent, such as methanol, tetrahydrofuran and mixtures thereof, at a temperature from about 25 * C to about 30. (:, about 1 to about 72 hours. In another In a preferred embodiment, the reductive amination reaction is completed by contacting compound 3 with excess ammonium acetate and excess trimethyl orthoformate (whichever is greater) in an inert diluent, such as 152_digas Alkane, the temperature from about 25.0 to about 30 ° C, for about 2 to about 72 hours, to form an imine intermediate. The sub-f 谙 first read the precautions on the back „Fill this page again}

____- 41-Z paper scale is applicable to Chinese National Su / μ Miscellaneous

Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Lijing 4 6 7 9 17 A7 A _ —______ B7 V. Description of the invention (39) ~ The amine intermediate is usually not separated, but is in contact with an excess of sodium samarium boride , Preferably about 1,2 to about 1 '5 equivalents of sodium hydride (whichever is greater). The resulting amine compound 5 can be easily purified by solid phase extraction with C18 silica gel. Pentane is used as the eluent. If necessary, the amine group formed by reductive amination can be used as a traditional brewing agent under traditional conditions. Brewing. The brewing agent usually has the formula L_ C (0) R6 ', where L is a leaving group, such as a halide, an activated ester, etc. β removes the laurel brewing group from compound 5, which is 5 and excess methoxide steel. In methanol and an inert diluent, such as dichloromethane, contact at about 25 to about 30 ° C. To about 24 hours. The reaction mixture aAmberlite IR-50S (H +) resin is neutralized to produce octaaminocycloheptylthione-galactopyranosin, B5. In one example, the primary amine group of compound B 5 can be tritiated as desired, that is, contacting B 5 with an excess of acetic anhydride in methanol containing a trace amount of water. Generally, this reaction is performed at about 25 * C to about 30 eC for 2 to about 24 hours to generate 3-ethylaminocycloheptylsulfanyl-ortho-galactophanol, C5 . In addition, the fifth-grade amine group can be fluorinated with phthalic anhydride, and then the lauryl group is removed to form 3- (2-carboxybenzylamino) cycloheptyl 2,3,4,6--methyl-0-lauroyl 1-thio-β-D · galactopyranoside, 6. This reaction is usually carried out by contacting Compound 5 with at least 1 molar equivalent, preferably an excess of phthaloyl field. Preferably, this reaction is carried out in anhydrous pyridine containing a catalyst amount of dimethylamino group. The reaction is usually in the range of about 251 to about 3 (about 12 to about 48 hours at rc to generate compound 6). And then the laurel is removed from 6. __ -42- This paper is clever. _ 家 " ^ 7 ^ 7 8 4 specifications (21GX297 mm) ~--(谙 Please read the notes on the back before filling in this page) Order printed by the Central Standards Bureau of the Ministry of Economic Affairs and printed by the Cooper Consumer Cooperative 4 6 7 9 17 a? ____ B7 V. Description of the invention (40) ~ fluorenyl, which is treated with sodium methoxide in methanol and an inert diluent, such as dichloromethane, 6 'at about 25T to about 30 ° C for about 1 to about 24 hours. Am * berlite IR -50S (H +) resin neutralizes the reaction mixture to produce 3- (2-carboxybenzylamido) cycloheptyl 1-thio-β-Dp galactose: y :, D5 〇 As shown in Figure 1 Compound 3 can also be reductively aminated with amino esters to form intermediates 7 or 8. In particular, compound 3 is preferably a third 'butyl ester' of β-alanine with a molar excess of 10 equivalents. (Based on 3) and at a concentration of at least 1 mole, preferably about 1.0 to about 1.2 equivalents of sodium cyanoborohydride. Typically, this reaction is carried out in a substantially anhydrous inert diluent. Such as acetonitrile, the temperature is about 25 * C to about 30 ° C, for about 1 to about 7 2 hours. The resulting intermediate 7 can be easily purified by solid phase extraction using C18 silicone gel, and pentanol is used as the eluent. Third of compound 7, the butyl ester group can be easily hydrolyzed to an equivalent carboxylic acid, and treated with 7 with an excess of silicon trifluoroacetic acid in an inert diluent, such as dichloromethane. This reaction is usually at about 2 5 ° C to about 30 ° C for about 1 to about 10 hours. The lauryl hydrazone of the carboxylic acid intermediate formed is removed, and sodium methoxide is used in methanol to form Nβ- [ΐ_ (ι_thio- β_χ > • galactopyranosyl) ¾hept-3-yl] -β-alanine, F5. In a similar manner, compound 3 can be reductively aminated with other amino esters, such as glycine III, Butyl ester, L-leucine tertiary, butyl ester, L-histamine methyl ester, L-tryptophan methyl ester, and L-arginine methyl ester to form intermediate 8. In these examples, The amino esters used are the third, butyl, and the third, butyl esters are dissociated with trifluoroacetic acid as described above to form Noc-Π- -43. Magic 97 (Please read the note on the back first to complete this page)

• m-HI Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 917. A7 —______ B7 V. Description of the Invention (41) '~~ (1-thio-β-D-galactopyranosyl) cycloheptyl _3_yl] _glycine, E5, and Nα- [1- (1-thio-pD-galactopyranosyl) cycloheptanyl] _L leucine, G5. In addition, in the case of using methyl urethane, the lauryl group of the intermediate 8 can be preferably removed first, and then 8 is treated with sodium methoxide in methanol, as described above. Next, the methyl ester of the amino acid portion is dissociated into a corresponding carboxylic acid, that is, treated with an excess of an aqueous lithium hydroxide solution for about 0.05 to about 2 hours. Neutralize the reaction mixture with Amberlite IR-50S (H +) resin to form Nα- [1- (1-thio-β-D-galactopyranosyl) cycloheptan-3-yl] · L_histidine , H5, Nα- [1- (1-thio-β-D-galactopyranosyl) cyclohepta-3-yl] -L-tryptophan, 15, and Nα- [1- (1-thio- β-Di galactopyranosyl) cycloheptan-3-yl] -L-spermine, J5. In addition, if desired, the base of the alcohol derivative, such as compound 4, can be converted to a leaving group, such as mesylate, tosylate, etc., and replaced with various nucleophiles. For example, treating an alcohol derivative with an excess, preferably from about 11 to about 15 equivalents of methanesulfanesulfonyl chloride in pyridine and an inert diluent, such as THF, can produce a comparable mesylate. The mesylate is then exchanged for example with azide steel to form a comparable azide derivative. This reaction is usually carried out by contacting methanesulfonic acid with an excess, preferably from about 5 to about 50 equivalents of sodium azide in an inert diluent, such as N, N · dimethylformamide, THF, and mixtures thereof. On, the temperature ranges from about 50 ° C to about 100 * C for about 1 to about 6 hours. Preferably, a crown ether, such as 18-crown ether-6, is added to the reaction mixture to facilitate the displacement reaction. The azide derivative is then reduced with a reducing agent to form a corresponding primary amine, ie, a compound such as 5. Preferably, the reaction is carried out by mixing an azide compound with about 1.0 to about 1.1 equivalents of sodium borohydride and about 2.0 to about 2.2 equivalents. -44- This paper size applies Chinese National Standard (CNS) A4 Specifications (210X29h > f) a '~~~ (read the notes on the back before filling in this page)

Printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 4 6 7 9 17 A7 —-------- B7 V. Description of the invention (42) The gasification chain (N1CI2) is in contact with an inert diluent, such as Ethanol, isopropanol or its quinone compound at temperatures from about 0. (: From about 0.5 to about 6.0 for about 0.5 to 6 hours. The above steps can be used to remove the lauryl hydrazone protecting group ^ In addition, amine compounds, such as 5, the primary amine group can be reduced by alkylation Further derivatization 'forms a secondary amine. Typically, this reaction is carried out by contacting the primary amine with an excess, preferably from about 2 to about 500 equivalents of aldehyde or ketone' and having at least one equivalent, preferably about 〖 0 to about 10 equivalents of a reducing agent, such as sodium triacetoxyborohydride. This reaction is usually carried out in an inert diluent, such as dichloromethane, methanol or a mixture thereof, at a temperature from about 0 to about 50 ° C 'lasts from about 10 to about 48 hours. In a preferred embodiment, the ketone used in this reaction is a cyclic ketone. Examples include: cyclobutadiene network such as 3, 3-dimethyl Cyclobutan-1-one; Cyclopentanone, such as 3,3-dimethylcyclopentan-1-one; Cyclohexanone and cycloheptanone. Then remove the lauryl group of the secondary amine formed, which is about to be lauryl A radical-protected compound is contacted with excess sodium methoxide in methanol and an inert diluent, such as dichloromethane, at about 25 ° C to about 3 ° C 1 to about 24 hours. Neutralize the reaction mixture with Am.berlite IR-50S (H +) resin to produce the desired secondary amine compound. As shown above, Figure 2 illustrates the synthesis of various dithiogalactose derivatives. α-halocarbonylcarbonyl compound, that is, 2-chlorocyclohexanone. As shown in FIG. 2, 1-S-ethenyl-2,3,4,6-methyl-o-lauroyl-1 is prepared as described above. -Thizone · D-galactopyranosyl, 2, reacts with 2-chlorocyclohexanone to form cyclohexanone-2-yl-2,3,4,6 -H-O-lauroyl—I-sulfur --Galactan, 9. The reaction is carried out with 2 and at least one equivalent 'better 10-1.2 equivalent -45-

Order (#Xianwen read the notes on the back and call away from this page)

The paper size is suitable for financial and economic standards (CNS) Λ4 Hao (mm) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 9 1 7 A? Γ ~ _____ B7 V. Description of the Invention (43) 2- Chlorocyclohexane is contacted and in the presence of excess dialkylamine, such as diethylamine. Typically, this reaction is performed in an inert diluent, such as dichloromethane, at a temperature from about -4 0 C to about 50 t for about 1 to about 6 hours to generate compound 90. Compound 9 is reused as above. 3 react with the same reagents and conditions to produce various 1-thiogalactose derivatives. In particular, compound 9 is reduced with sodium hydrogenate to form 10, which, after removal of the lauryl group, can generate 2-hydroxycyclohexyl 1-thio-β-D-galactopyranosyl, A2. In addition, compound 9 can be reductively aminated with ammonium acetate and sodium cyanoborohydride to form intermediate 11. After removing the lauryl group, it can form 2-aminocyclohexyl 1-thio-β-D-pyran Galactose tincture, b 2. Compound B 2 can be further treated with acetic anhydride to generate 2-acetamidocyclohexyl 1-thio_p_D_galactopyranoside, C 2. In addition, the intermediate 11 can be fluorinated with phthalic anhydride to form intermediate 12. The lauryl group is removed under the above conditions to generate 2- (2-carboxybenzylamidinylcyclohexyl 1-thio-β-D-anan. Galactose: g :, D2. In addition, compound 9 can utilize β-alanine third, butyl ester reductive amination to form intermediate 1 3, which is then deprotected to form Nβ _ [卜 (1-thio -β-D-galactopyranosyl) cyclohex-2-yl] -β-alanine. In addition, compound 9 may be other amino acid esters, such as glycine. Third, butyl, L- Leucine third, butyl ester, L-histamine methyl ester, l-tryptamine methyl ester, and L-arginine methyl ester, reductively aminated to form intermediate 14, which can be formed once deprotected Να- [1- (1 · thio-β-Dp galactopyranosyl) cyclohexan-2-yl] -glycine, Ε2, Να- [1- (1-thio-β-Ι) _ρΛnan Lactosyl) cyclohex-2-yl] -L-leucine, G2, Ntx- [l- (14b_p_D- _-46-1 ^^^ Applicable to Chinese national standard ^ (〇 阳) 8 4 specifications (210 / 297 male feet) ~~~~-(谙 Please read the notes on the back before filling out this page) -Order 4 b / 9 1 7 • A7 B7 r * _ ---------- One, five, invention (44) p-galactopyranosyl) cyclohex-2-yl] -L-histidine, H2, Nα- [1- (1-thio-PD-galactopyranosyl) cyclohex-2-yl ] -L-tryptophan, 12, and Nα- [1- (1-thio-β-D-galactopyranosyl) cyclohex-2-yl] -L-spermine, J2. If necessary, a 1-thiogalactose derivative of the formula I, in which γ is a sulfide chain (-S) can be oxidized using conventional reagents and conditions to generate equivalent fluorene (Y = -S (0)-) And Qi! (Y = -S〇2_) derivatives. Examples of suitable reagents for oxidizing sulfide compounds to sulfonium include: hydrogen peroxide, peracids such as 3-chloroperoxycarboxylic acid (MCPBA), sodium periodate, sodium chlorite, sodium hypochlorite, and secondary gas. Calcium Acid, Tertiary Butyl Hydrate, etc. It is also possible to apply a palmar oxidizing agent (an optically active reagent) to provide a palmar subarsenic. This protogenic reagent is well known in the art and includes reagents as described in Kagen et al. 7 and referenced therein. The oxidation reaction printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs is usually carried out by contacting a 1-thiogalactose derivative with about 0.95 to about 1.1 equivalents of an oxidizing agent in an inert diluent such as digas methylbenzene. 0 ec to about 50 ° C for about 1 to about 48 hours. The resulting thallium can be further oxidized to a comparable thallium, that is, the thallium is contacted with at least one equivalent of an oxidizing agent, such as hydrogen peroxide, MCPBA, potassium permanganate, and the like. Alternatively, rhenium can be prepared directly by contacting the sulfide with at least 2 equivalents, and preferably with an excess of an oxidizing agent. In a similar manner, a 1-thiogalactosyl derivative of formula I, in which R4 is -XR5, X is sulfur and R5 is a well-defined substituent other than hydrogen, can be oxidized to form a comparable sub wind (X = -S ( 0) _) and Qi (x = _s〇2_) derivatives. In addition, if you want, the hydroxyl group of galactose part can be used to confirm the steps and -47- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 Gong Ao) ~ ~ Printed by the Shell Industry Consumer Cooperative of the Central Elevator Bureau of the Ministry of Economic Affairs Poly 4 S79 1 7 Α7 Β7 V. Description of the invention (45)

The I reagent is easily digested, fermented, or phosphorus fermented to produce a compound of formula I where at least Ra'Rb, which is -0-S02-0H, -C (0) R10,-^ (0) (011 ^ ) 2 or a pharmaceutically acceptable salt thereof, wherein R10 and R11 are as defined above. This tritiation reaction can be the most phase step in the synthesis (that is, the use of an acyl halide, such as laurenyl chloride, as described above) or a transformation effect after the synthesis of a compound of formula I, wherein Ra, Rb, R ° and Rd are each hydrogen Uses such as hydrazone, anhydride, halophosphate, sulfur trioxide, etc. For example, the deblocked hydroxyl group can be further tritiated, that is to say, the compound containing the radical is in excess, preferably about K1 to about 1.2 equivalents of Emei: sulfur trioxide treatment, in an inert diluent, such as N, N- Metformamide is at ambient temperature for about 1 to about 24 hours. Typically, the resulting sulfate (i.e., -0-S 0 2-0 H) is separated in its salt form, that is, treated with Na + resin in an inert diluent such as methanol. Further reaction conditions suitable for the formation of sulfates and phosphates can be found in, for example, US Patent No. 5,5 8 0, 8 5 8 8 In another embodiment of the present invention, the 1-thiogalactose of the present invention The derivative may be adhered to a carrier, preferably a solid carrier, or via a galactose moiety, or via a fraction derived from a Michael acceptor, or an alpha-halocarbonyl compound. The method for attaching a compound to a carrier via various functional groups is well known in the art, and any of these known methods can be used to covalently attach the 1-thiogalactose derivative of the present invention to a carrier. By way of example, the 1-thiogalactose derivative of formula I, in which R4 contains a carboxylic acid moiety, can be covalently attached to an aminated solid phase support using conventional coupling steps and reagents. Typically, this coupling reaction is carried out with well-known coupling reagents, such as carbodiimide, BOP reagent (benzotriazol-1-yloxy-tris (di-48-). ) Α4 Regulations (210X297 public splash) ------------..} (谙 Please read the notes on the back before filling this page) Order ^ 4 6 7 9 17 Α7 Β7 V. Description of the invention (46) Mono-methylaminofluorophosphonic acid scale), etc. β Suitable carbodiimides include examples via dicyclohexylcarbodiimide (DCC) 'diisopropylcarbodiimide, (3-dimethyl Aminopropyl) _3-ethylcarbodiimide (EDC), etc. Preferably, well-known coupling initiators can also be used in the reaction mixture, such as N-methylsuccinimide, 1-hydroxybenzotris Azole and others to promote the coupling reaction. The coupling reaction is usually carried out with a solid support and an excess, preferably about 11 to about 10 equivalents of the 1-thiogalactose derivative (depending on the equivalent number of amine groups on the solid support Standard) and at least 1 equivalent, preferably about 15 to about 3.0 equivalents of the coupling reagent (based on the 1-thiogalactose derivative), in an inert diluent Such as N, N-dimethylformamidine, etc. If desired, a coupling initiator can be used in the reaction to the equivalent of 'preferably about 1.5 to about 3.0 equivalents (based on the 1-thiogalactose derivative) For example, the base is trivalent. Generally, the temperature at which the coupling reaction proceeds is from about 0. (: to about 50. {:, about 24 to about 100 hours. Once the reaction is complete, the solid support is preferably with an excess of Acetic anhydride is contacted in methanol at a temperature from about (TC to about 40 ° C) for about 12 to about 24 hours to mask any unreacted amine groups on the solid support. 1-thiogalactose derivatives are incorporated The yield of the solid-phase support can be determined using well-established procedures, as described by ^ Dubois et al. 9. The 1-thiogalactose derivative of the present invention can also be prepared on the solid-phase support via solid-phase synthesis technology. .Typically, this solid phase technique involves covalently attaching a 1-thiogalactose compound to a solid support via the hydroxyl groups on the galactose moiety, using traditional procedures and reagents. Covalently bonded 1- The thiogalactose compound is then combined with an α, β-unsaturated carbonyl compound or an α-halocarbonyl using the above steps. Reduction or reduction of intermediates containing carbonyl groups. -49- This paper size applies to Chinese National Standard (CNS) M specifications (210X297 mm)-I I-1. (谙 Please read the precautions on the back before reading (Fill in this page) Order printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy 4 Printed by the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China Du printed 6 7 9 彳 7 A? ___________B7 V. Description of the invention (47) " It can be aminated to form alcohol or amine compound, which can be further derivatized as described in the above. "By way of example, 1-dithioethyl-β-D _galactopyranosylpyridine can be easily adhered to disulfide-based gas resins. It has an active gas of about 0.80 to about 1.00 millimolar per gram, and the resin is contacted with about 0,75 to about 2.0 equivalents of 1-dithiohexyl-β-D-galactopyranosyl pyridine in pyridine, It also contains a catalyst amount of 4- (N, N-diamidoamino) pyridine, and the temperature ranges from about 25 »c to about 100C for about 12 to 48 hours. The free state thiol group at the covalently bonded galactose position is generated through the treatment of the resin with dithioerythritol (clelaild, s reagent) and triethylamine in an inert diluent, such as methanol. About 6 to 24 hours at ambient temperature. The 1-thio_ {3-〇_galactopyranosaccharose generated can be reacted again as described above to form ^ thiogalactose of the formula [I] covalently adhered to the solid phase carrier resin. If desired, the i-thiogalactose derivative can be dissociated from the solid support resin by contacting the resin with an excess of trifluoroacetic acid and triisopropylsilane in an inert diluent, such as digasmethane 'at ambient temperature. Utilization In one embodiment, the compounds of the present invention can be used to block the binding of toxins, such as heat labile enterotoxin or cholera toxin, to their receptors in a test tube or in vivo. In another specific example, the compound of the present invention can inhibit the binding of organic toxins (such as bacteria, viruses, bacillus, etc.), such as Vibrio cholerae or Escherichia coli, to its cell surface receptors. Therefore, the compounds of the present invention can be used to alleviate conditions associated with infections in organisms, including gastrointestinal infections caused by enterotoxic organisms, such as enterotoxin producing strains of Vibrio cholerae or Escherichia coli, including the following: Liu-50- This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297mm) •, · (Please read the precautions on the back before filling in this 1)

A7 B7 46791 7 V. Description of the Invention (Juvenile) Blood, abdominal pain, etc. When used to treat or alleviate this condition, the compounds of the present invention are usually delivered to patients in need of such therapy. Pharmaceutical compositions can be utilized which contain a pharmaceutically acceptable diluent and an effective dose of at least one compound of the present invention. The dose of the compound to be administered to a patient varies depending on which compound and / or composition is administered, the purpose of administration such as prevention or treatment, the condition of the patient, the manner of administration, and the like. In therapeutic applications, the composition is administered to patients already suffering from this infection, such as gastrointestinal infections related to the enterotoxigenic strains of Vibrio cholerae or Escherichia coli, at a dose sufficient to at least partially arrest the disease and its complications Of the symptoms of the disease-onset. A dose sufficient to accomplish this is defined as a "therapeutically effective dose." The effective dose for this purpose depends on the judgment of the physician, based on factors such as the degree or severity of the patient's infection, the age, weight, and general condition of the patient. Well, for therapeutic applications, the compounds described herein are administered in a range of from about 0.1 to about 10 mg / kg / day. The pharmaceutical composition may contain more than one compound of the invention. For example, it may contain one Compounds of formula I are highly effective in inhibiting the binding of LT, and different compounds of formula I are highly effective in inhibiting the binding of enterotoxin producing strains of Escherichia coli to their cell surface receptors. When a carrier is used, When the compound of formula Γ is attached to treat or relieve conditions related to gastrointestinal infections, a non-toxic, mechanically and chemically resistant carrier is preferred. It can pass through the intestine without being affected, and can be administered orally The carrier which is completely and quickly eliminated afterwards is the best, so this kind of carrier can provide the rapid elimination of toxins and / or pathogens from the individual. The composition type is administered to the patient, -51-This paper size is applicable to the Chinese National Standard (CNS) A4. (210 X 2 to 7 mm) (Please read the precautions on the back before writing this page)

Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 9 17 A7 B7 V. Description of the Invention (49) Printed by the Shell Standard Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics It is printed by various routes, including oral, transanal, and transdermal , Subcutaneous, intravenous, intramuscular, etc. These compounds are effective as injectable and orally deliverable pharmaceutical compositions. This composition is prepared 'in a manner well known in the pharmaceutical arts and contains at least one active compound. The pharmaceutical composition is down-regulated in the presence of a pharmaceutically acceptable carrier. In preparing the composition of the present invention, the active ingredient is usually mixed with an excipient and diluted or closed with the vehicle in this carrier, which can be in the form of capsules, foamable granules, paper or other containers. When the excipient is used as a diluent, it may be a solid, semi-solid or liquid substance, which may be used as a vehicle, carrier or medium for the active ingredient. Therefore, the composition can be in the form of lozenges, pills, powders, dragees, foaming granules, cachets, elixirs, suspensions, emulsions, solutions, syrups, etc., containing up to 10% wt% Active compounds, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Examples of suitable excipients include: lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia 'calcium scale acid, alginate, tragacanth' gelatin, dream acid, microcrystalline fiber Vegetarian, polyvinylacetate P copper, cellulose, sterile water, syrup and methyl cellulose. The blend also contains: lubricants such as talc, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; preservatives such as methyl and propyl parabens; sweeteners; and aromatics Agent. The composition of the present invention can be blended to provide rapid, sustained, or delayed release after the active ingredient is administered to a patient. The 1-thiogalactose derivative of the present invention can also be administered in a prodrug form, that is, it can be converted into a biologically active compound of formula I in the form of a derivative in vivo. Prodrugs typically include compounds of formula I, where Ra, Rb, and ruler. OR -52 This paper size is applicable to Chinese National Standard (CNS) A4 is now standard (210X29 * 7mm) 谙 First notice of the subscription fee A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 0 = Egypt bd = Wide Bimodal bs = broad unimodal BSA = bovine serum albumin d = bimodal dd = two bimodal DMAP = dimethylamino eq- = equivalent g = grams L = state m = multimodal · meq = milli-equivalent mg = Milligram mL = milliliter mmol = millimolar N = equivalent concentration OPD = ortho-phenylenediamine PBS = phosphate buffered saline at pH 7.2 q. = Four quint. = Five peaks s = unimodal · t = Three peak TFA = THF trifluoroacetic acid = THF -53- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297) 4 6 79] 5. Description of the invention (so)

At least one of Rd is a biologically labile group, such as _P (〇KO〇 ") 2, and R1I is as defined above. ) Issue m1 to illustrate the invention, and do not intend to limit the scope of the invention in any way. Unless otherwise stated, all temperatures are in degrees Celsius. Example :: In the example, the following abbreviations have the following definitions. If the abbreviation is ambiguous, there is usually an acceptable definition (read the ethics on the back before filling out this page)

A7 B7 467917 V. Description of the invention (51) TLC = thin layer chromatography

Tween 20 = polyoxyethylene sorbitan monolaurate ML = microliter iH-Nmr spectra were recorded with a Brueker AM-3 60 spectrophotometer, and MALDI-TOF (the spectrum is based on HP G2 02 0 A (LD-TOF) Recorded by the instrument. The optical rotation was detected by a Perkin-Elmer 241 polarimeter. The reaction was tracked by TLC in silicone FG 254 (E. Merck, Darmstadt, Gefmany).

Example A Solid Phase Extraction of Laurel Tritiated Intermediates As shown in the following examples, some interphases of laurel tritiated reactions were purified by solid phase extraction. In this purification step, the reaction mixture was concentrated, redissolved in methanol, and applied to C18 silica (Waters Prep C18, 125 people, printed by the Consumer Cooperative of the Central Bureau of Prototype of the Ministry of Economic Affairs, 1 g per 20 mg of lauryl base Carbohydrate) ^ C18 precious stones were washed with methanol (10 ml / g C18 silica) and the product was dissolved with pentane (10 ml / g C18 dream stone). Regarding the compound containing L-arginine, the reaction mixture was concentrated, redissolved in 70% methanol, and applied to (: 18 silica. (: 18 hard rock was washed with 70% methanol, and the product was dissolved in methanol. The resulting The product contains no residual reagents and can be determined by TLC, h-nmr or MALDI-TOF mass spectrometer.

Example B Round 1, 2, 3, 4, 6 · Wu-0-Laurel base-α-D-i »Reproduction of 1-galactose (3.78 g, 21.0 mmol), pyridine (50 Ml), and a suspension of 4-dimethylamine p-pyridine (catalyst amount) in pentamole (150 ml), under argon atmosphere, add lauryl chloride (50 ml, 210 mmol), at- 54- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297 mm) 4 6 7 9 1 A7 B7 Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (52) -7 8 ° C . The mixture allowed it to reach ambient temperature. The resulting white slurry slowly dissolves and forms a detailed precipitate of the p ratio bond hydrochloride. After 40 hours, the pyridinium hydrochloride was filtered off and the pentane solution was concentrated. Column chromatography (Si02, pentane / EtOAc 9: 1) yields 1 (16'0 g, 70% yield), [a] D25 + 39 ° (c 0.9, CHC13), i-Nrar data (CHC13 ): δ 6.39 (d, 1H, J 2.4 Hz, Hl), 5.51 (br s, 1H, H-4), 5.35 (m, 2H, H-2 and H-3), 4.32 (br t, 1H, J 6.6 Hz, H-5), 4.08 (d, 2H, J 6.6 Hz, H-6a and H-6b), 2.39, 2.3 8, 2.30, 2.26 (4t, 2H each, J 7.5 Hz, -CH2CO -), 2.21 (m, 2H, -CH2CO-), 0,88 (t > 15H, J 7.0 Hz, -CH3). Analyze CaHmO ": C, 72.2; H, 11.3. Measured radon: C, 72.6; radon, 1 11 5.

Example C Synthesis of 1-S-Ethyl-2,3,4,6-cyclo-0-lauroyl-l-thio-pD-galactopyranosyl (2) Method 1: For Compound 1 (from Example B , 1 g, 0.91 mmol) and thiol acetic acid (0.4 ml, 9.1 mmol) in anhydrous digas methane (5 ml), boron trifluoride etherate (1.7 ml, 13.6 millimoles). After 10 minutes the cooling bath was removed, after 24 hours it was diluted with dichloromethane, washed with saturated sodium bicarbonate, dried over sodium sulfate and concentrated. Column chromatography (_8102, pentane 120 / £ 1: 0 eight (: 9: 1: 1) yields 2 (0.60 g, 70% yield). Method 2: For compound 1 (from the example, 2 7 6 _ 5 mg, 0.2 5 3 mol) in anhydrous tetrahydrocondensation (2.0 ml), benzylamine-55 was added under argon- This paper size applies Chinese national standard {CNS) A4 specification {210X297 (Mm) (#Please read the note on the back, and then fill out this note) Order A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (53) (27.9 microwells, 0.255 millimoles). The mixture was concentrated after 70 hours. The residue was dissolved in anhydrous dioxane (4.0 ml), and under argon, trichloroacetonitrile (250 μl, 2,5 mmol) and i, 8-diazinebicyclo [5.4.0] Undec-7-ene (30 μl, 0.2 mmol). After 3 hours, the mixture was concentrated and the residue was rinsed through a short column (SiO 2, pentane / EtOAc 19: 1) and concentrated. To the residue in anhydrous dichloromethane (3.5 ml) under argon, t-thiol acetic acid (1 ml 96 hours later, the reaction mixture was concentrated, and the residue was purified by column chromatography (Si02, pentane, EtOAc 19: 1) Can produce 2 (90 mg, 37% yield), [a] D25 + 21 ° (c 1, CHC13), iH-Nmr data (CHC13): δ 5.47 (d, 1H, J 3.4 Ηζ, Η-4), 5.32 (t, 1H, J 10.0 Hz, H-2), 5.25 ((1, 1H, J 10.0 Hz, Hl), 5.12 (dd, 1H, J 3.4 and ⑺-❹! ^ ,! ! -3), 4'08 (m, 3H, H-5, H_6a and H-6b), 2.14_2'43 (m, 8H, -CH2C0-), 2.37 (s, 3H, -SAc), 0.88 ( t, 15H, J 7-O.Hz, -CH3) 〇 Analytical estimation C56H102O1 () S: C, 69.5; H, 10.6; S, 3.3. Measured radon: C, 69.4; H, 10.8; S, 3.5. Method 3: To compound 1 (2 0.0 g, 1 8.2 mmol) and thioacetic acid (5.0 ml, 1.9 equivalents) in anhydrous dichloromethane (300 ml) under argon, add trifluoromethane at 0 ° C Trimethylsilyl sulfonate (5.0 ml, 0.5 equivalent). Remove the cold water bath immediately, and after 48 hours the mixture was diluted with digas methane, washed with saturated sodium bicarbonate, and dried ( Na2S04) and concentrated. Column chromatography (Si02, pentane / EtOAc 20: 1) yields 2 (13.7 g, 77% yield), [a] D25 + 21 ° (c 1, CHC13), l- ' Nmr data (CHC13): δ 5.47 (d, 1H, J 3.4 Hz, Η- -56-This paper size applies to China National Standard (CNS) A4 specification (210 X 2 ~ 7 mm)---··· (Please read the note on the back before filling out this page} Order printed by the Consumers Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 467917 A7 ___ B7 V. Invention Description (54) 4), 5.32 (t, 1H, J 10.0 Hz, H- 2), 5.25 (d, 1H, J 10.0 Hz, Hl), 5.12 (dd, 1H, J 3.4 & 10.0Hz, H-3), 4.08 (m, 3H, H_5, H-6a and H-6b) , 2.14-2.43 (m, 8H, -CH2CO-)? 2.37 (S > 3H, -SAc), 0.88 (t, 15H, J 7.0, Hz, -CH3). Analyze and estimate CwHmOwS: C, 69.5; H, 10.6; S, 3, 3 0 Measured 値: C, 69.4; H, 10 · 8; S, 3.5. Example C 'Synthesis of 1-8-Ethyl-2.3.4,6-"0-lauryl-1-thio-00-0 dipyranose lactose Method 1: Compound 1 (20.0 g, 18.2 mmol Mol) and thioacetic acid (27.0 mL, 20 eq) in anhydrous toluene (80 mL), and tin (IV) chloride (21.3 mL) was added dropwise at room temperature under argon. The response chased carefully with Tic. After 1 hour, 600 ml of a 1 M HC1 aqueous solution was added to the vigorously stirred mixture, and the resulting mixture was filtered through Celite to remove the tin salt emulsion. The mixture was diluted with pentane (800 ml), washed with water (2 × 400 ml), saturated sodium bicarbonate (300 ml) and water (300 ml), dried over Na 2 SO 4 and concentrated. The residue was purified three times by column chromatography (Si02, pentane / EtOAc 20: 1, 30: 1, 40: 1) to produce 1-S-ethenyl-2,3,4,6-z--0- Lauryl-1-thio-α-D-galactopyranosyl (3.65 g, 21%). W-Nmr data (CHC13): δ 6.26 (d, 1H, J 5.5 Hz, Hl), 5.47 (dd, 1H, J 11.0 Hz, 5.5Hz, H-2), 5'46 (d, 1H, J 3.5 Hz, H-4), 5.04 (dd, 1H, J 11.0 Hz, 3.5Hz, H-3)? 4.17 (t, 1H, J 6.5 Hz, H-5), 4.06 (d, 2H, J 6.5 Hz, H-6a and H-6b), 2.38 (t, -57- This paper size applies Chinese National Standard (CNS) A4 Regulations (21 OX297 mm) ------ ^ ----—— First News Read the note on the back # ^ 项 再 镇 write this page} -Order _ Printed by the Central Bureau of Standards of the Ministry of Economic Affairs and Consumer Cooperatives 679 ”A7 ____________B7___ V. Invention Description (55)., 8H, J 7.0 Hz, -COCH2- ), 2.40 (s, 3H, -SAc), 0.87 (t, 15H, J 7'0 Hz, -CH3). Method 2: For compound 1 (25.0 g, 22.9 mmol) and thioacetic acid (8 5 ml, 114.5 mmol) in dry dichloromethane (100 mL), and trifluoromethanesulfonyltrifluorosilyl silane was added at room temperature under argon atmosphere. After 20 hours, the mixture was dichloromethane ( (600 ml), diluted with saturated sodium bicarbonate (250 ml) and water (2 x 200 ml), dried over Na2SO4 and concentrated. The residue was purified three times by column chromatography (Si 02, pentane / EtOAc, 20: 1, 30: 1, 40: 1) can produce 1-S-ethynyl-2,3,4,6-methyl-lauroyl-sulfur-a-D- Galactopyranosyl (1.59 g, 7.2%).

Example D General Michael's Addition and a-halocarbonyl Substitution for Compound 2 (1 mmol) and Electrophile (1.2 mmol) in anhydrous digas methane (8 ml) under argon After adding Et2NH (4 mL) for 1-3 hours, the mixture was concentrated, and the residue was purified by silica gel column chromatography using SiO 2 and dissolved in pentane / EtOAc. The products were identified by 1H-nmr spectrometer and MALDI-TOF mass spectrometer.

Example E. General procedure for reduction to alcohol. For the product of Example D (1000 micromolar) in anhydrous tetrahydrofuran (2.0 mL) and isopropanol (0.7 mL), add NaBH4 (150 micromolar under argon). ). After 0.5-3 hours, the mixture is concentrated, acetic acid (approximately 40 microliters) is added (in some cases before concentration) and the residue is in accordance with the solid of Example A-58-This paper is compliant with national standards (CNS) Specifications (210X297 public attack) '(Please read the precautions on the back before filling out this page) Order Λ Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 4 S 7 9 1 7 a7 B7 V. Description of the invention (56) Purified by extraction step. The product alcohol was identified by 1H-nmr spectrometer and MALDI-TOF mass spectrometer.

Example F. General procedure for reduction to sexual amination to primary amine Method 1: The product of Example D (100 μmol) and ammonium acetate (75 mg, 1 mmol) in anhydrous methanol (2.3 mL) and tetrahydrofuran (0.05 9 ml) and NaCNBH3 (100 μmol) was added under an argon atmosphere. After 1-72 hours, the mixture was concentrated and the residue was purified according to the solid phase extraction procedure of Example A. The product amine was identified by 1H-nmr spectrometer and MALDI-TOF mass spectrometer. Method 2: The product of Example D (200 mg, 0.198 mmol) and anhydrous NH4OAc (30 mg, 0.4 mmol) in anhydrous MeOH (6 mL), anhydrous 1,2 · dichloroethane (6 mL ) And trimethyl orthoformate (1 ml), and stirred under argon for 24 hours (until TLC analysis showed that most of the starting material was consumed). NaBH4 (10 mg, 0.26 mmol) was added and the mixture was concentrated after 1 hour. The residue was purified according to the solid phase extraction procedure of Example A to form a primary amine (containing a trace amount of an equivalent alcohol). This mixture was dissolved in pentamidine / Et 'OAc (l · 1)' and applied to a Waters Sep-Pak Plus Longbody SiO2 cassette. The cassette was washed with pentane / EtOAc (1: 1,20 mL) (to remove the equivalent alcohol), and then dissolved in toluene / EtOH (9: 1, 30 mL) to generate primary amine.

Example G The general procedure for the fluorination of primary amines with phthalic anhydride is from Example F. O-laurate fluorinated primary amines (100 μMole), malaria (2.7 mmol) and 4- (N, N-dimethylamine Base) Pyridine (catalyst amount) soluble in non-_59- This paper size is applicable to the national standard of China (CNS > A4 size (210x29 ·; public 漦)) (This page)

4 6 7 9 彳 7 A7 ________B7 Five 'Explanation of invention (57) in water pyridine. The mixture was concentrated after 12-48 hours, and the residue was purified according to the solid phase extraction procedure of Example A. The product 2-carboxybenzidine was identified by iH-nmr spectrophotometer and MALDI-TOF mass spectrometer. Example 一般 General procedure for amino acid reductive amination The product of Example D (100 μmol) and the third amino acid, butyl ester hydrochloride or methyl ester hydrochloride (1 mmol) in anhydrous MeCN (2.25 ml) and THF (0.75 ml), NaCNBH3 (100 micromolar) was added. After 1-72 hours, the mixture was concentrated and the residue was purified according to the solid phase extraction procedure of Example A. The N-alkylated amino acid of the product a was identified by a 1H-nmr spectrophotometer and a MA.LDI-TOF mass spectrometer.

Example I General Procedure for Deblocking Alcohol To Example E, lauryl alcohol (100 micromolar) in anhydrous methanol (7.1 ml) and digas methane (1.4 ml), methanol sodium sodium methoxide was added under argon atmosphere. (1M, 50 μl). After 1-24 hours, the mixture was neutralized with Amberlite IR-50S (H +) resin, filtered and concentrated. The residue was dissolved in water and applied to a C18 silica column (Waters Prep C18, 125, 5 g). The C18 silica was washed with water (50 ml), and the product was dissolved in 70% methanol (50 ml). The alcohol produced was identified by a j-nmr spectrophotometer and a MALDI-TOF mass spectrometer.

Example J General steps for blocking primary amines For Example F, the laurylated primary amines (1000 micromoles) in anhydrous methanol-60 were used in this paper. Chinese paper standard {CNS > A4 size (21〇χＭ7 (Public Note) (Read the note on the back, and then fill out this page), ΤΓ printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 9 17 Α7 _______ Β7 5. Description of the invention (58) (7.1 ml) and Dichloromethane (1.4 mL) was added with sodium methoxide (1M'50 μl) under argon. After 1-24 hours, the mixture was neutralized with Amberlite IR-50S (H +) resin, filtered and concentrated. The residue is dissolved in dichloromethane / methanol 2: 1 »and added to waters PrePak Plus

Longbody Si02 box. The box was washed with dichloromethane / methanol (2: 1), and the product was dissolved with two gas methane / methanol / water (5: 5: 1) (20 ml) and concentrated. The residue was dissolved in water and packed into a C18 silica column (Waters Prep C18, 125A, 5 g). C18 silica was washed with water (50 ml), and the product was dissolved in methanol (50 ml). The generated primary amine was identified by iH-nmr spectrophotometer and MALDI-TOF mass spectrometer.

Example K General procedure for N-ethylation of primary amine f jj. Example J primary amine (100 micromolar) was added to moist methanol (4.4 ml) and acetic anhydride (0.4 ml) was added. The mixture was concentrated after 2 to 4 hours, redissolved in water and added to C18 chopping stones (Waters Prep C18, 125A, 5 g). C18 precious stones were washed with water (50 ml) and the product was dissolved in methanol (50 ml). The resulting acetamidine was identified by a 1H-nmr spectrophotometer and a MALDI-TOF mass spectrometer. Printed by the Central Bureau of Standards, Ministry of Economic Affairs, 4 Consumer Cooperatives

Example L. General procedure for blocking 2-famidylamine. 0-Laurylpyridinyl 2-Chrysyl from Example G; amidine (100 μmol) in anhydrous methanol (7.1 ml) and diamine. Pyridoxane (1.4 ml) and methanolic sodium methoxide (1 M, 50 µl) were added under argon. After 1 · 24 hours, the mixture was neutralized with Amberlite IR-50S (Η +) resin, filtered and rolled and shrunk. -61-This paper size applies to Chinese National Standard (CNS) A4 specification (2! 0 > < 297 mm) A7 B7 Printed by Shellfish Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs 4 6 7 9 17 59) ~~~: The residue is dissolved in methane / methanol (8: 1;), and then applied to a Waters PrePak Plus Longbody Si02 box. The box was washed with digas methane / methanol (8: 1), and the product was dissolved in digas methane / methanol / water (65: 35: 5) (20 ml) and concentrated. The residue was dissolved in water and packed into a C1 8 hard stone column (Waters Prep C 18, 125, 5 g). The C 18 hard stone was washed with water (50 ml), and the product was dissolved in methanol (50 ml). . The resulting 2-aminobenzidine was determined by an iu-nmr spectrometer and a MALDI-TOF mass spectrometer. Example M General procedure for blocking alkylated glycine, β-propylamine and L-leucine compounds Example N-alkylated amino acid Third, butyl ester (100 micromolar) to Trifluoroacetic acid (3.5 ml) was treated in anhydrous dichloromethane (3.5 ml) for 1-10 hours. N-propyl acetate (8 ml) and toluene (16 ml) were added and the mixture was concentrated, and then concentrated twice with toluene. To the residue was added anhydrous methanol (7.1 ml) and dichloromethane (1.1 ml), and methanolic sodium methoxide (1M, 200 µl) was added under an argon atmosphere. After 1-24 hours, the mixture is neutralized with Amberlite IR-50S (H +) resin, filtered and concentrated > the residue is dissolved in dichloromethane / methanol (9: 1) and added to Waters SepPak Plus Longbody Si02] E. The cartridge was washed with dioxane / methanol (9: 1), and the product was dissolved with digas methane / methanol / water (65: 3 5: 5) (20 ml), and the residue was concentrated and dissolved in water, and then applied to C18 seconds stone column (Waters Prep C18, 125, 5 g) ° C18 silica was washed with water (50 ml), and the product was dissolved in 70% methanol (50 ml). The generated 1 ^ -alkylated glycine -62- The paper size is in accordance with the Chinese National Standard (CNS) A4 specification (2iOX297 male f) (Please read the cautions on the back before filling this page)

4 6 7 9 1 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economy Mass spectrometer identification.

Example N General procedure for deblocking N-alkylated L-syrosine and L-tryptophan compounds. Example Η N-alkylated methyl amino acid (1000 micromolar) in anhydrous methanol (7.3 ml) and dichloromethane (1.1 ml). Methanolic sodium methoxide (1 M, 50 µl) was added under an argon atmosphere. After 1-24 hours, the mixture was neutralized with Amberlite IR-50S (Η +) resin, filtered and concentrated. The residue was dissolved in 70% methanol 'and applied to a ci8 silica column (Waters Prep C18, 125A, 5 g). The product was then dissolved in 70% methanol (50 ml). To the residue was added water (3.7 ml) of an aqueous lithium hydroxide solution. ! ^, 0.3 ml). After 0.5-2 hours, the mixture was neutralized with Amberlite IR-50S (H +) resin, filtered and concentrated. The residue was dissolved in dichloromethane / methanol (9: 1) and then added to a waters SepPak Plus Longbody SiO2 box. The box was washed with dichloromethane / methanol (9: 0), and the product was then dissolved and concentrated with methanol / water (65: 35: 5) (20ml). The residue was dissolved in water and added to C18 silica column (Waters Prep C18, 125A, 5 g). C18 silica was washed with water (50 ml) and the product was dissolved with 70% methanol (50 ml). The resulting N-calcined L-histamine Acid, L-tryptophan compound was identified spectrophotometrically with 111-111111 'and ^ 8 101-1'0? Mass spectrometer. Example 0 General steps to block N-alkylated L · arginine compounds_ -63- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (谙 Please read the notes on the back before filling in this page) Order fr · 4679] 7 A7 B7 China History Standards Bureau, Ministry of Economic Affairs Printed by a consumer cooperative V. Description of the invention (61) Example N-alkylated methyl arginine (100 micromolar) in anhydrous methanol (> .3 ml) and dichloromethane (1.1 ml) ), Add methanol to sodium methoxide (1 M, 50 µl) under argon atmosphere. After 1-2 4 hours, the mixture is neutralized with Amberlite IR-50S (Η +) resin and filtered Concentrated. The residue was dissolved in 70% methanol, then added to a C18 silica column, and the product was dissolved in 70% methanol (50 ml). To the residue was added lithium hydroxide (1M) in water (3.7 ml). , 0.3 ml). After 0.5-2 hours, the mixture was neutralized with Amberlite IR-50S (H +) resin, filtered and concentrated. The residue was dissolved in water and charged into a C18 silica column (Waters Prep Cl ^ , 125, 5 g). C18 silica was washed with water (50 ml), and the product was dissolved in 50% methanol (50 ml). The N-calcined-spermine acid compound formed was measured by 1H-nmr spectrophotometry. Identification by MALDI-TOF mass spectrometer.

Example P General procedure for the preparation of mesylate: For the alcohol from Example D (0.3 millimolar) in anhydrous tetrahydrofuran (2 ml) and anhydrous pyridine (4 ml), methanesulfonium gas (0. 5 ml). After 12 to 24 hours, the mixture was washed with 0.5 M H CI and extracted with pentane. The pentane extract was concentrated and the residue was purified on C18 silica to form a mesylate derivative.

Example Q General procedure for the preparation of azide compounds. The mesylate from Example P (0.2 mmol) was added to anhydrous DMF (8 mL) and anhydrous THF (3 mL). Sodium nitride (5 mmol) and 18-crown-6 (180 mg). After 2 hours, the reaction mixture was 64- (Please read the notes on the back before filling this page) The size of the paper used for this edition is applicable to the Chinese National Standard (CNS) 210X297 public address. Explanation of the invention (62) The potassium compound is concentrated, and the residue is purified on C18 silica. In some cases, the product is rechromatographed on silica gel using pentane / EtOAc (9: 1) as the eluent to form an azide derivative.

Example R General procedure for reduction of azide to primary amine To the azide compound of Example S (15 μmol) was added to a solution of anhydrous isopropanol (1 ml) and absolute ethanol (1 ml) in an argon atmosphere. NaBHdl5 micromolar) and NiCl2 (30 micromolar). After 1 hour, the reaction mixture was neutralized with acetic acid (1 drop), concentrated and purified on C18-silica to produce "" grade amines. Example s The general steps of primary amine reductive calcination. For the primary amine of Example F or S (6.8 micromolar) in anhydrous methanol (iml) and anhydrous digas methylbenzene (1ml), add it to the knee or Rim (34 millimoles) and sodium triacetoxyborohydride (47 micromoles). After 24-48 hours, toluene (1 mL) was added and the mixture was concentrated and the residue was purified on c 1 8 silica gel.

Example T General procedure for reductive amination of the product of Example D (0.1 mmol) and primary amine (045 mmol) in anhydrous monochloromethane (2 ml), methanol (2 ml) and triethyl orthoformate After adding NaCNBH3 (1 millimolar) β under argon for 24 hours, the mixture was concentrated and dissolved in toluene (1 ml) and purified on Cl8_silica gel) 0 ______ _ 65 "

{CNsT.A «(210X297 ^ tT {Please read the notes on the back before filling this page) Order 4679 | 7 A7 I ——----------- 5. Description of the invention (63)

Example U The general procedure for deblocking secondary amines. For the secondary amines from Examples S or T or 0-Lauryl sulfonated secondary amines (100 μMole) in anhydrous methanol (7.1 ml) and digas methane (1.4 ml), Under argon atmosphere, methanolic sodium methoxide (1 M, 50 µl) was added. After 1-24 hours, the mixture was neutralized with Amberlite IR-50S (Η +) resin, filtered and concentrated. The residue was dissolved in dichloromethane / methanol 2: 1 and added to Waters SepPak Plus Longbody Si02E. g was washed with dichloromethane / methanol (2: 1), and the product was dissolved with dichloromethane / methanol / water (5: 5: 1) (20 ml) and concentrated. The residue was dissolved in water and refilled. It was added to a C18 silica column (Waters Prep C18, 125 persons, 5 g). C18 silica was washed with water (50 ml), and the product was dissolved in methanol (50 ml). The secondary amine formed was identified by j-Nmr spectrophotometer and MALDI-TOF mass spectrometer. Example A1 Printed and synthesized by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2-Cyclopentyl-1-yl 1-thio-β-Dp galactopyranoside 隹 According to steps D, E and I above to prepare the title compound, use 2-Air cyclopentamin is an electrophilic agent. The mass spectrum data are as follows: M (estimated 値): 280.34; M (measured 値): 304.9 (M + Na +) »The selected tnmr data is as follows: ^ -nmrCCDaOD): δ 4.4 4 (Η -1), 4.4 2, 4.3 8 and 4_35. _ Example A2 Synthesis of 2-Ethylcyclohex-1-yl1-thio-galactopyranosyl: According to steps D, E and I above, the title compound was prepared, and 2-cyclocyclohexyl-66- China National Standards (CNS) A4 specification (210X297 mm) 4 Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs_ B7 V. Invention Description (64) is electrophilic. Mass spectrum data are as follows: M (estimated): 294 34; M (found): 318.8 (M + Na +). The selected nmr data is as follows: ^ -nmrCCDsOD): δ 4.55 (Η-1) »4.43 4 39 and 4.34. Example A3 Synthesis of 3-Ethyl-1-phenylbut-1-yl 1-thio-β-D-galactopyranosyl: y: According to steps D, E and I above, using 4-phenylbut-3 -En-2-one is an electrophilic agent. Mass spectrum data are as follows: M (estimated 値): 345.43; M (found 値): 368.0 (M + Na +). The selected nmr data is as follows: 1 ^; -nmr (CD 3 〇D): δ 4 · 4 5 (Η -1), 4.4 3, 4.3 1 and 4.2 5 〇 Example A4 Synthesis (3- 2-yl) methyl 1-thio-β-Dp galactopyranosyl: y: The title compound was prepared according to steps D, E, and I above, using 3-methylene • 2-n-suto entertainment • ketone as electrophile Agent. Mass spectrum data are as follows: M; (estimated 値): 3 2 0.4 1; M (found 値): 344.6 (M + Na +). The selected nmr data is as follows: iH-nmi ^ CDsOD): δ 4.30 (H-1) and 4.29. Example A 5 Synthesis of 3-Hydroxycyclohept-1-yl 1-thio-β-D-galactopyranosyl. The title compound was prepared according to steps D, E, and I above, using cycloheptyl-1 · ketone as an electrophile Agent. The mass spectrum data are as follows: M (estimated 値): 3 08.40; M (found 値): 332.1 (M + Na +). The selected nmr data is as follows: 1H-nmr (CD3OD): δ 4,394 (Η · 1), 4.389 and 4.381. Example A51 -67- This paper size applies to Chinese national standards (CNS > Λ4 size (210 × 297 mm) (谙 Please read the notes on the back before filling this page) Order printed by the Central Consumers Bureau of the Ministry of Economic Affairs, printed by the Consumer Cooperatives 4 6 7 9 17 A7 ____ __B7 V. Description of the Invention (65) Synthesis of 3-Ethylcycloheptan-1-yl 1-thio-α-Dp galactopyranosyl. A. Prepare the title compound according to steps D'E and I above, using 1 -8_Ethyl 1-2,3,4,6 -Lauryl-1-thio-a-Dp galactopyranoside (from Example C 'above) and cyclohepten-1-one are electrophilic The mass spectrum data are as follows: M (estimated 値): 3 08.40; M (measured 値): 33 j 3 (M + Na +). The selected nmr data is as follows: ^ -nmr (CD3OD): δ 5.44 (d, J 5. 8 Hz, Hl) and 5.45 (< 1, J 5'8 Hz, Hl) 0. Example A 6 Synthesis of 2,2-dimethyl-4-hydroxycyclopent-1-ylthione -β-D -galactopyranosylpyrene According to steps D, E and I above, the title compound was prepared using 4,4 · dimethylcyclopent-2-en-1-one as the electrophile. The mass spectrum data is as follows: Μ (estimated 値): 3 08.40; Μ (measured 値): 3 32.1 (M + Na +). The selected nmr number The data are as follows: 1H-nmr (CD3OD): δ 4_34 (H-1), 4.315, 4.310, and 4.305 ° Example A7 • Synthesis of 3-hydroxycyclopent-1-yl 1-thio-β-D-galactopyranoside制备 The title compound was prepared according to steps D, E and I above, using cyclopent-2-en-1-one as the electrophile. The mass spectrum data is as follows: M (estimated 値): 280.34; M (measured 値): 3 04.9 (M + Na +). The selected nmr data is as follows: 111-111111 '(0〇30〇): 8 4.36 (11-1), 4.3 5 5 and 4.34. Example A8 -68-This paper size applies Chinese national standards (CNS) Α4 specification (210 × 297 males) (Please read the precautions on the back first and then fill in & this page)

Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 4 6 7 9 17 A? B7 V. Description of the invention (Qiu) Synthesis 4-Jing 2-1 -sulfur-β-D-p galactopose In step D, E and I above, the title compound was prepared using pent-3-en-2-one as the electrophile. The mass spectrum data are as follows: M (estimated 値): 282.3 5; M (found 値): 305,3 (M + Na +). The selected nmr data is as follows: W-nmr ^ CDaOD): δ 4 · 42 (Η-1), 4.41 and 4.3.9 »Example A 9 Synthesis of 2,2-dimethyl- 5- # fluorenylcyclohexane_ «; [-Yl1-thio-β-Dp galactofen according to steps D, E and I above to prepare the title compound, using 4,4-dimethylcyclohex-2-en-1-one as Electrophilic. Mass spectrum data are as follows: μ (estimated 値): 322.42; M (measured 値): 346.6 (M + Na +). The selected nmr data is as follows: ^ -nmriCDsOD): δ 4.34 (Η · 1), 4.33 and 4.32. t Example A1 0 Synthesis of 3-ylcyclohexane " 1-yl1-thio-β-Dp galactopyranosyl: y: The title compound was prepared according to steps D, E, and I above, using cyclohex-2-ene The mass spectrum data of 15-keto as an electrophile 15 are as follows: M (estimated 値): 294.37; M (found 値): 317.3 (M + Na +). The selected nmr data is as follows: iH-iimriCDsOD): δ 4,422 (Η · 1), 4.417 and 4.38. Example A 1 1 'Synthesis of 4,4_dimethyl_3-hydroxycyclohexyl-χ-yl 1-thio-β-D-galactopyranosyl-69-This paper is applicable to China National Standards (CNS) A4 size (210 X 29? Mm) ((Please read the precautions on the back before filling in this page)

6 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs? 9 1 7 at -__ B7 V. Description of the invention (67) The title compound was prepared according to steps D, E and I above, using 6,6_dimethylcyclohexane- 2-Dilute '-1- 嗣 is an electrophilic agent. Example B 1 Synthesis of 2-aminocyclopent-1-yl-1-thio-β-Digalactopyranosyl · ig: The title compound was prepared according to steps D, F and J above, using 2-chlorocyclopentanone For electrophiles. Mass spectrum data are as follows: M (estimated 値): 279.36; M (found 値): 376.3 (M + Η +). The selected nmr data is as follows: ^ -nmrCCDaOD): δ 4.4 6 (Η -1), 4 · 4, 5, 4, 3 7 and 4.27. Example B2 Synthesis of 2-aminocyclohex-1-yl1-thio-β-Dp galactose: y: The title compound was prepared according to steps D, F, and J above, and 2-cyclohexidine was used as the electrophile Agent. Mass spectrum data are as follows: M (estimated 値): 293.38; M (found 値): 295.8 (M + H +). The selected nmr data is as follows: 1H-nmr (CD3OD): δ 4.48 (Η-1), 4.44, 4.40 and 4.30. Example B 3 Synthesis of 3 · Amino-1-phenylbut-1-yl1-thio-galactopyranosyl: y: The title compound was prepared according to steps D, F and J above, using 4-phenylbut-3- Enenone is an electrophile. Mass spectrum data are as follows: m (estimated radon): 344.45; M (measured radon): 345.1 (M + H +). The selected ^ machi data are as follows: ^ -nmrfCDsOD): δ 4.41 (Η-1), 4.12 and 3.90. Example B4 -70- This paper size applies to Chinese National Standards (CNS) M specifications < 210 × 2 mm) '':-(Read the precautions on the back before filling in this page)

C Ψ © £ Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (68) Synthesis of (3-amino-n-pyridine_2-yl) methyl 1_thio_β _ [)-ΐί galactophan标题 Prepare the title compound according to steps D, F, and J above, using 3-methylene-2 -n-conetanone as the electrophile. Mass spectrum data are as follows: μ (estimated 値): 319.42; M (measured 値): 321.6 (M + Η +). The selected nmr data is as follows: iH-nmrfCDsOD): δ 4,42 (Η · 1), 4.41, 4.38 and 4.35. Example B 5 Synthesis of 3-aminocycloheptan-1-yl 1-thio_β_D_galactopyranosyl. The title compound was prepared according to steps D, F and J above, using cyclohept-2-ene-1- Ketones are electrophiles. Mass spectrum data are as follows: M (estimated 値): 307.41; M (found 値): 3 3 3.0 (M + Na +). The selected nmr data are as follows: 111-111111 '(€ 00300): 3 4.41 (11-1), 4.39 and 4.3.8. Example B 6 Synthesis of 2,2-dimethyl-4-aminocyclopent-1-yl 1-thio · β-D-pyranolose. The title compound was prepared according to steps D, F and J above, using 4,4-dimethylcyclopent-2-en-1-one is an electrophilic agent. Mass spectrum data are as follows: M (estimated 値): 307.41; M (found 値): 307.2 (M + Μ +). The selected nmr data is as follows: W-nmi ^ CDsOD): δ 4.35 (Η · 1), 4.33, 4.32 and 4.30 〇

'' Example B 6 A Synthesis of 2,2-dimethyl-4-(methylamino) -cyclopent-1-yl 1-sulfur-β-D-galactopyranoside-71-This paper is applicable to China Standard (CNS) Α4 size (210X297 mm) (read the precautions on the back before filling out this page)

467917 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (69) Prepare the title compound according to steps D, T and U above, using 4,4-dimethylcyclopent-2-ene-1 -Ketone is an electrophile, and β-mass spectrometry data using methylamine as the primary amine is as follows: M (estimated 値): 3 2 1 _ 4 3; M (measured 値): 322.7 (M + Η +). The selected nmr data is as follows: 1 H-nmr (CD3OD): δ 4.325 (H-1), 4.315, 4.308, 4.3 04 β Example B 6 Β Synthesis of 2,2-dimethyl-4- (isopropylamino) Cyclopenta-fluorenyl- 1-thio-β-D-galactopyranosamine was depleted according to steps D, T and U above to prepare the title compound using 4,4-dimethylcyclopent-2-en-1-one Is an electrophilic agent, and isopropylamine is a primary amine. Mass spectral data are as follows: M (estimated 値): 3 4 9 4 8; Μ (found 値): 350.7 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4/460 (Η-1), 4.401, 4.400, 4.391.

Example B6C Synthesis of 2,2-dimethyl-4- (n-propylamino) cyclopentyl-; i_, 1-thio-β-D-galactopyranosyl The title compound was prepared according to steps D, T and U above In addition, 4,4-dimethylcyclopentan-2-one-1-one is used as the electrophile, and main propylamine is used as the primary amine. Mass spectrum data are as follows: M (estimated radon): 349.49; M (measured radon): 350.5 (M + H +). The selected nmr data is as follows: 1 H-nmr (CD3OD): δ 4.324 (Η-1), 4.317, 4.3 1 0, 4.3 07.

Example B6D Synthesis of 2,2-Dimethyl-4-((10-Second-Butylamino) cyclopent-1-yl-1-thio-β-D-galactopyranosyl-72- wood paper scale Applicable Chinese National Standards (CNS) such as specifications {210X297 mm) (Please read the note on the back before filling this page) Order 4S7 917 A7 B7 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ) Prepare the title compound by following steps 骒 D, T, and U, using 4,4-dimethylcyclopent-2-en-1-one as the electrophilic preagent, and (R)-(a) _second Butylamine is a primary amine. Mass spectrum data are as follows: M (estimated 値): 364.52; M (measured 値): 364'6 (M + Η +). The selected data nmr is as follows: ιΗ-nmr (CD3〇D): δ 4.328 (Η-1), 4.319, 4.313, 4.31 Example B6E Synthesis of 2,2-dimethyl-4-((S) -second , Butylamino) cyclopent-1-yl 1-thio-β-Dp galactopyranosyl. The title compound was prepared according to steps D, T and 17 above, using 4,4-dimethylcyclopentane-2缔 -1-Ming is an electrophilic agent 'and (S)-(+)-Second, butylamine is a primary amine. Mass spectrum data are as follows: M (estimated 値): 364.52; M (found 値): 364.6 (M + Η +). The selected nmr data is as follows: in-nmr (CD3OD): δ 4 · 3 3 3 (Η-1), 4.3 30, 4.3 00, 4.290. Example B 6 F Synthesis of 2,2-dimethyl-4- (pent-3-ylamino) cyclopentyl · fluorenyl-1-thio-β-D-galactopyranosyl iridium according to steps D, T and U The title compound was prepared using 4,4-dimethylcyclopent-2-en-1-one as the electrophile and 3-pentamine as the primary amine. Mass spectrometry data are as follows: M (estimated ：): 3 77.5 3; M (found 値): 376.7 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4.333 (Η-1), 4.329, 4.300, 4.290. Example B 6 G Synthesis of 2,2-dimethyl-4- (n-hexylamino) cyclopentyl-l- -73 (Please read the precautions on the back first to fill in this page)

•• IT This paper standard is applicable to China National Standards (CNS) A4 regulations (21 OX 297 mm) 4 6 7 9 Economy • Which Central Standard Bureau employee consumer cooperatives printed A7 B7 V. Instructions issued (71 bases) 1-Sulfur-β-D-galactopyranosyl: y: The title compound was prepared according to steps D'T and U above, with 4,4-dimethylcyclopentan-2-one-1-one as the electrophile And n-hexylamine are primary amines. The mass spectrum data are as follows: M (estimated 値): 3 9 1.5 7; M (measured 値): 394.3 (M + Η +). The selected inmr data is as follows: CD3OD): δ 4,3 3 6 (H-1), 4.3 32, 4.303, 4.291 0 • Example B 6 Η Synthesis of 2,2 ·· dimethyl-4- (cyclobutyl-l · · aminoamino) Cyclopentyl 1-yl l-thio-β-D-galactopyranoside: g: The title compound was prepared according to steps D'T and U using 4,4-dimethylcyclopent-2-en-1-one as The electrophile 'and cyclobutylamine are primary amines. The mass spectrum data are as follows: Μ (estimated 値): 3 6 1 · 50; Μ (measured 値): 361 · 6 (Μ + Η +). Selected nmr data It is as follows: lH_nmr (CD3OD): δ 4.315 ()-1), 4.300, 4.292, 4.290 〇 Example B 61 Synthesis of 2,2-dimethyl 4- (3,3-Dimethylcyclobutylamino) Cyclopent-1-yl1-thio-β-Dp is less galactose than according to steps D'T and U. The title compound is prepared using 4,4_ Dimethylcyclopenta-2-en-1-one is an electrophilic agent, and 33-difluorenylcyclobutane- 丨 -ylamine is a primary amine. The mass spectrum data is as follows: M (estimated): 389 5 5; (Measured 値): 392.2 (M + H +). The selected nittr data is as follows: nmr (CD3〇D): δ 4.324 (Η-1)} 4.311, 4.305 4.294. '

Example B6J -74- This paper size applies to Chinese National Standard (CNS) A4 (210x297 male 1) (Please read the precautions on the back before filling this page)

Printed by Zhengong Consumer Cooperative, Central Standards Bureau of the Ministry of Economic Affairs 4 8 TS 1 7 · A7 __ __ B7 V. Description of the invention (72) Synthesis of 2,2-dimethyl-4- (cyclopentan-1 · ylamino) ring戌 _ 1-yl 1-thio-β-D-galactopyranoside is prepared according to the above steps D, T and U, using 4,4-dimethylcyclopent-2-en-1-one as Electrophilic agents and cyclopentylamine are primary amines. Mass spectral data are as follows: M (estimated 値): 3 7 5. 5 2; Μ (measured 値): 376.6 (M + Η +). The selected nmr data is as follows: IH_nmr (CD3OD): δ 4.322 (H-1), 4.310, 4.304, 4.295.

Example B6K Synthesis of 2,2-dimethyl-4- (cyclohex-1-ylamino) cyclopent-1-yl 1-thio-β-D-galactopyranoside U The title compound was prepared using 4,4-dimethylcyclopent-2-en-1-one as the electrophile and cyclohexylamine as the primary amine. Mass spectrometry data are as follows: M (estimated ：): 3 89.5 5; M (found 値): 391.2 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3〇D): δ 4.319 (Η · 1), 4.310, 4.307, 4.293 »

Example B6L Synthesis of 2,2-dimethyl-4- (4-methylcyclohexyl-1-ylamino) cyclopent-1-yl1-thio-β-D-galactopyranoside according to step D above , T and U to prepare the title compound, using 4,4-dimethylcyclopent-2-en-1-one as the electrophile, and 4-pyridylcyclohex-1-ylamine as the primary amine. The mass spectrum data are as follows: M (estimated 値): 403.47; M (found 値): 404.8 (M + Η +). The selected nmr data is as follows: 1 H-nmr (CD3〇D): δ 4.33 3 (Η-1), 4.3 12, 4.300, 4.295 «

Example B 6 Q -75- This paper size applies the Chinese National Standard (CNS) M Regulation (210X297).

4 6 7 9 17 Printed by A7 B7, Shellfish Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (73) Synthesis of 2,2-dimethyl-4- (3-methylcyclopentyl-; [• amino ) Cyclopentyl-1 -yl 1-sulfur-β-D-ρ galactose. The title compound was prepared according to steps D, T and U above, using 4,4-dimethylcyclopent-2-ene-1 -Ketone is an electrophilic agent, and 3 · methylcyclopentylamine is a primary amine. The mass spectrum data are as follows: M (estimated 値): 389.55; M (found 値): 390.7 (M + Η +). The selected nmr data is as follows: in-nmr (CD3OD): δ 4.3 8 3 (H-1), 4.325, 4.300, 4.292.

Example B 6 R Synthesis of 2,2 " Dimethyl-4- (3,3-dimethylcyclopentyl_1-ylamino) Cyclopentan-1-yl-1-sulfur-β-D-p Lactose: y: Prepare the title compound according to steps D, T and U above, using 4 4 -dimethylcyclopent-2-en-1-one as the electrophile, and 3,3_dimethylcyclopentane_ The mass spectrometry data of "I-ylamine is primary amine" is as follows: M (estimated 値): 4 295; M (found 値): 404.3 (M + Η +). The selected nmr data is as follows: lH_ nmr (CD3OD): δ 4.3 22 (H-1), 4.3 05, 4.300, 4.295 >

Example B 6 T Synthesis of 2,2-dimethyl-4- (3-methylcyclohexyl · h-aminoamino) Wang Mupentyl-1-yl 1-thio-galactopyranosyl. ^ Follow step D above , T and U to prepare the title compound, and 4,4-dimethylcyclofluorene-2-associate-1-fluorene as an electrophilic agent 'and 3-methylcycloimidamine as the primary amine. Mass spectrum data are as follows: M (estimated 値): 403 57; M (found 値) .: 404.8 (M + H +). The selected nmr data is as follows: (CD3OD): δ 4.326 (Η-1), 4.313, 4.303, 4.294. 76- The paper size of the table applies the Chinese National Standard (CNS) Α4 regulation (2 丨 OX 297 feet) (read the note on the back first and then fill out this page)

467917 A7 B7 Printed by the Consumer Cooperatives of the Central Bureau of Quasi-Staff of the Ministry of Economic Affairs 5. Description of the Invention (74) Example B 7 • Synthesis of 3-Aminocyclopentyl-1_yl1_thio_0 _!) _ Galactopyranoside Steps D, F and J were used to prepare the title compound. The mass spectrometry data using cyclopent-2-ene rim as an electrophile was as follows: M (estimated 値): 279.35; M (measured 値): na The selected nmr data is as follows: ijj -nmr (CD3OD): S4.46, 4.40, 4.38 & 4.34 (4d, J10Hz), 3.88 (br s), 2,61, 2.27, 2.15, 1.82 and 1.64 (5 m). Example B 8 Synthesis of 4-Aminopentyl-2-yl 1-thio-p-D-galactopyranosyl. The title compound was prepared in steps D, F, and J, with pent_3_ene_2__ as the parent The electron mass spectrum data of the electron agent are as follows: M (estimated 値): 28 1.37; M (found 値): 283.4 (M + H +). The selected nmr data is as follows: ιΗ_ nmr (CD3OD): S4.41 (H-1), 4.40 & 4.36. Example B 1 0 Synthesis of 3-Aminocyclohex-1-yl1-thio_p_D-n galactophan The title compound was prepared according to steps D'F and J above, using cyclohexan_2_asso_ 1- Ketones are electrophiles. Mass spectrum data are as follows: M (estimated 値): 293.38; M (found 値): 317.9 (M + Na +). The selected nmr data is as follows: W-nmr (CD3〇D): δ 4.54 (Η-1), 4 52 4.49 and 4.47 ° * Example B 1 1 Synthesis of 3-amino-4,4-dimethyl Cyclohexanyl 1-thio-β-D-galactopyranosyl The title compound was prepared according to steps D, F, and J above, using the 6} 6-dimethylformate 77- table paper standard applicable Chinese National Standard (CMS) Α4 specifications (2 丨 0X297mm) ----------- (Please read the precautions on the back before filling this page} 、 1Τ 4 6 7 9 17 A7 B7 V. Description of the invention (75) Cyclohex-2-en-1-one is an electrophilic agent. Example C 1 Synthesis of 2-Ethylamino-pentyl-1-yl-1.thio-galactopyranoside. The title was prepared according to steps D, F, J, and K. Compound, using 2-air-cyclopentan-1 ketone as electrophile. The mass spectrum data are as follows: M (estimated 32): 32 1.39; M (found 値): 345.8 (M + Na +). The selected < nrar data is as follows : W-nmr (CD3OD): δ 4.53 (H-1), 4.44 4.32, and 4.24. Example C2 Synthesis of 2-ethylethylaminocyclohex-1-yl1-thio-β-Dp galactopyranoside The title compound was prepared in D, F, J and K using 2-chlorocyclohexane-1-one as the electrophile. The mass spectrum data are as follows M (estimated 値): 33 5.42; M (measured 値): 3 59.4 (M + Nf). The nmr number selected is as follows: W-nmr (CD3OD): δ 4.43 (Η-1), 4.42 4.32 And 4.29. Example C 3 Synthesis of 3-acetamido-1-phenylbutyl 1-sulfuryl-β-D-P galactophan The naked compound D, F, J and K were prepared as described above, 4_Phenylbutene 3 -ene-2__ was used as the electrophile. The mass spectrum data are as follows: μ (estimated 値): 3 86.48; M (measured 値): 408.3 (M + Na +). The selected nmr data is as follows : IH-nmr (CD3OD): δ 4.32 (Η · 1), 4 25 4.38 and 3.79. Example C 5 -78- This paper size applies Chinese national standard (Oyang to 4 specifications (210 > < 297 mm) 467 9 17 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (76) ~~ Synthetic 3 -ethylaminoamine heptyl-l-yl-thio-β-D-njt galactose According to the above steps D, F, J and K to prepare the title compound, using cyclohept-2-propan-1-one as an electrophile. The spectrum data are as follows: m (estimated 値): 349 · 42; M (Measured 値): 3 72.5 (M + Na +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4 · 403 (Η-1), 4.3 97, 4.34 and 4.33. Example C 7 Synthesis of 3-Ethylaminopentyl-1-yl 1-thio_p_D-p galactose can be prepared according to steps D'F, J, and K above, using cyclopenta-2 · 晞1-one is an electrophilic agent. Mass spectrum data are as follows: m (estimated radon): 3 2 1.3 9; M (measured radon): 349.5 (M + Na +). Example C 8 Synthesis of 4-Ethylaminocyclopent-2-yl-1.sulfur-β-Dp galactopyranoside. The title compound was prepared according to steps D, F, J, and K above, using 戍 _3_ene-2 -Bream is electrophilic. Mass spectrum data are as follows: m (estimated radon): 323.40; M (measured radon): 347.7 (M + Na +). The selected nmr data is as follows: W-nmr (CD3OD): δ 4.42 (Η · 1), 4.38 4.3, 7 and 4.35. Example C 1 0 Synthesis of 3-acetamidocyclohexyl 1-thio-β-D-galactopyranosyl. The title compound was prepared according to steps D, F, J and K above, using cyclohex-2-ene-1 -Ketones are electrophiles. Mass spectrum data are as follows: m (estimated radon): 3 3 5.42; M (measured radon): 3 73.7 (M + Na +). The selected nmr data is as follows: ^ -nmr (CD3OD): δ 4.52 (Η-1), 4.464 and. -79- 7-^---"(#First read the notes on the back to complete this page)

、 1T 0-^ ΓΗ. This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297mm) A7 B7 467917 V. Description of invention (77) 4.45 5. Example C 1 1 Synthesis of 3-Ethylamine-4,4-dimethylcyclohexyl '1-sulfur-β-D · galactomannan according to steps D, F, J and JC above to prepare the title compound, 6,6-Dimethylcyclohex-2-en-1-one was used as the electrophile. Example D 1 Synthesis of 2- (2-Chictyloctylamino) cyclopent-1-yl-1-sulfo-β-Di »galactopyranosyl: y: The title was prepared according to steps D, F, G and L above. The compound uses air cyclopentan-1-one as an electrophile. The mass spectrum data are as follows: M (estimated 値): 42γ.47; M (measured 値): 450.5 (M + H +) »The selected 111 ^ data are as follows: iH-nmr (CD3OD): δ 4.69 (Η · 1), 4.58 4.27 and 4.22. '' Example D 2 Synthesis of 2- (2-Chlorylamino) cyclohex-1-yl 1-thio-β-Dp galactopyranoside. The title compound was prepared according to steps D, F, G and L above, 2 Chlorocyclohexane-1-one was used as the electrophile. The mass spectrum data are as follows: M (estimated 値), 441.50; M (measured 値): 465 · 9 (M + NO. The selected nmr data is as follows: h-nmr (CD3OD): δ 4.54 (H-1) 4 52 4.50 and 4.35. Example D 3 Synthesis of 3- (2-carboxyamido) -1 · phenylbutyl-80- Each paper size applies Chinese National Standard (CNS) A4 (210X 297 mm) (please first M) Read the notes on the back and write this page again) -s Shellfish Consumer Cooperatives, Lili 4S7917 A7 B7-, 丨 丨 * ----- Ⅴ. Description of Invention (78) ~~ -1- 1-thio-β-D-p-galactopyranophene was prepared according to the above steps D'F, G and L using the phenylphenyl-3-en-2-one as electrophile. Mass spectrometry data As follows: M (estimated 値): 492.56; M (measured 値): 513.0 (M + Na +). The selected nmr data is as follows: W-ninr (CD3OD): δ 4.41 (Η-1), 4.115 4.110 And 3.90 ° Example D 4 Synthesis of [3- (Leptidylpyridinylamino) -n-Sulfur_2-yl] methyl 1-sulfur-β-D-p-galactopyranosyl, according to step D'F'G above And L to prepare the title compound, using 3-methylene-.2-n-pentanone as the electrophile. Spectral data are as follows: M (estimated 値): 467.54; M (measured 値): 492,9 (M + Na +). The selected nmr data is as follows: iH-nmr (CD3〇D): δ 4.39 (H-1 ), 4.34, 4.3 1 and 4.26. Example D 5 Synthesis of 3- (2-Leptyl Ethylamino) cycloheptan-1-yl 1-thio-β-D-galactopyranoside according to steps D, F, G and L were used to prepare the title compound, using cyclohept-2-en-1-one as the electrophile. The mass spectrum data are as follows: M (estimated 値): 453.52; M (found 値): 479.6 (M + Na +). The inmi · data was selected as follows: ^ -nmr (CD3OD): δ 4.53 (H-1), 4.51, 4.42 and 4.40. Example D8 Synthesis of 3- (2-carboxyamido) pent-2-yl-81-Ben Paper; ^ Applicable Chinese national standard {CNS specification (210X297 mm)

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

Order (谙 Read the precautions on the back before filling in this j

4 6 7 9 17 Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention (79) 1-Sulfur-β-D-galactopyranosyl, prepared according to steps D, F, G and L above The title compound uses pentamidine-3-bream-2 as the electrophile. The mass spectrum data are as follows: M (estimated 値): 429.48; M (found 値): 452,7 (M + Na +). The selected nmr data is as follows: j-nmr (CD3OD): δ 4.42 (H-1) 4 41 4.4.0 and 4,35. Example D 9 Synthesis of 5- (2-Ethylamidoamido) -2,2-dimethylcyclohex-1-yl 1-thio-β-Dp galactopyranoside In accordance with steps D, F 'above G and L were used to prepare the title compound, using 4,4_-methylcyclohex-2-yl-1-pyrene as an electrophile. The mass spectrum data are as follows: M (estimated 値): 469.55; M (measured 値): 492_4 (M + Na +). Example D 1 0. Synthesis of 3- (2-carboxybenzylamino) cyclohexyl-l-yl 1-sulfur-β-D-galactopyranosyl: y: prepared according to steps D, F'G and L above The title compound, and cyclohex-2-en-1-one as an electrophile. The mass spectrum data are as follows: μ (estimated 値): 441_50; centimeters (measured 値): 11 ”. The selected 11-cho data are as follows: 111_ nmr (CD3OD): δ 4.37 (Η-1), 4-34, and 4.32 . Example E 1 Synthesis of Ntx- [2- (l-sulfur-β-Dp galactopyranosyl) cyclopent-1-yl] glycinate according to steps D, VII and M to prepare the title compound using 2-chlorocyclopentane -i_ Ketone is an electrophilic agent, and the third is glycine, butyl ester, amino ester Mass spectrometry -82-t Paper size applies to Chinese National Standard (CNS) M specifications (210X297 mm) (谙 Read the precautions on the back before writing this page}

According to #Ministry of Central Standards Bureau, Consumer Consumer Cooperatives, India 467917 A7 ____B7 V. Description of the invention (80) 'The data is as follows: M (estimated): 3 3 7.3 9; M (measured): 3 59.8 (M + Na + ). The selected nmr data is as follows: (CD3OD): δ 4.44 (Η_1), 4.41, 4.40, and 4.34. Example E 2 Synthesis of Ncx- [2- (l-sulfur-β-D-p-galactopyranosyl) cyclohex-1-yl] glycinate according to steps D, IX and M to prepare the title compound, and using 2- Gas cyclohexane-1-one is an electrophile and third is glycine, and butyl ester is an amino acid ester. Mass spectral data are as follows: M (estimated 値): 351.42; M (measured 値): 3 53.5 (M + H +), 376.5 (M + Na +). The selected nmr data are as follows: iH-nmr (CD3OD): δ 4 · 48 (Η-1), 4.47, 4.36, and 4.29. Example E 3 Synthesis of N α-[4-phenyl-4-(1-thio-β-D-galactopyranosyl) but-2-yl] glycinate according to steps D, VII and M to prepare the title compound, Use 4-phenylbut-3-en-2-one as the electrophile and the third glycine, and the butyl ester is the amino ester. The mass spectrum data are as follows: M (estimated 値): 4 0 1.4 8; Μ (measured 値): 40 3. · 1 (M + Η +). The selected nmr data is as follows: W-nmr (CD3OD): S4.29 (H-1), 4.18, 3.92 & 3.91. Example E 4 Synthesis of Nα- [3-((1-thio-β-D-galactopyranosyl) methyl) ortho-2-yl] glycine according to steps D, VII and M to prepare the title compound, using 3-Methylene-2-n-83-This paper size applies to China National Standards (CNS) Α4 size (210X297) (Please read the note on the back first and then fill out this page) Order 'f 6 4 7 9 彳 7 A7 B7 Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs Du Yinbag 5. Description of the invention (81 ketone is an electrophile, and glycine is the third, and butyl ester is the amino acid vinegar. The mass spectrum data is as follows: M (Estimated 値): 3 77.46; M (measured 値) · · 401.4 (M + Na +). The selected nmr data is as follows: iH_nmr (CD3OD): δ 4.42 (Η · 1), 4.40, 4.383. 4.377, and 4.3_5. Example E 5 Synthesis of Nα- [3- (1-thio-galactopyranosyl) cycloheptan-1-yl] glycinate The title compound was prepared according to steps D, VII and M, using cycloheptene 2_ The ketone is an electrophile and the third is glycine, and the butyl ester is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 365.45; M (measured 値): 3 67.4 (M + Η +) , 3 89.9 (M + Na +). Selected!! Machi data Bottom: j-nmr (CD3〇D): δ 4.46 (Η-1), 4.45, 4.42, and 4.3_8. Example E 5 ^ Synthesis of Να " [3- (1-thio-ot-D-ι »ratio Galactosyl) cycloheptan-1 -yl] glycinate to prepare the title compound according to steps D, VII and M above, using 1-S-ethylfluorenyl-2,3,4,6-methyl-0 laurel 1-thiogalactosyl (from the example CV above), cyclohept-2-en-1-one is an electrophile, and glycine is the third, and butyl ester is the amino ester. The mass spectrum data is as follows: M ( Estimated 値): 365.45; M (measured 値): 366.6 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 5.51 (d, J 5.5 Hz, H-1 (mainly ) 5,46 (d, J 5.5 Hz, Hl), 5.47 (d, J 5.5 Hz, 84) Wood paper size applies Chinese National Standard (CNS) A4 specification {210X297 mm) (Please read the precautions on the back first Fill out this page again).

., 1T Ψ T 1 467 9 1 7 A7 ____ B7 _ 5. Description of the invention (82) H-U secondary)), 5.48 (d, J 5.5 Hz, H-1). (#Please read the notes on the back before filling this page) Example E 6 Synthesis of Nα- [4,4-dimethyl_3- (1_thio_p_D-galactopyranosyl) cyclopent-1-yl] Glycine was prepared according to steps D, VII and M, using 4,4-dimethylcyclopentan-2-en-1-one as the electrophile, and glycine as the third and butyl ester as the amine group. Acid ester. Mass spectral data are as follows: M (estimated 値): 3 6 5 · 4 4; Μ (found 値): 368.0 (M + Η +). The selected ninr data is as follows: W-nmr (CD3OD): S4'33 0 (H-1), 4.325, 4.32 (^ 4.30o • Example E 7 Synthesis of Nα- [3- (1-sulfur-β- D- t1 galactopyranosyl) cyclopent-1-yl] glycinate to prepare the title compound according to steps D, VII and M above, using cyclopent-2-en-1-one as an electrophile, and glycine Third, butyl ester is an amino ester. The mass spectrum data are as follows: M (estimated 値): 3 3 7, 3 9; M (measured 値) · 360.9 (M + Na +). The selected nmr data is as follows: iH-nmr (0〇〇〇〇): 5 4.38 (11-1), 4.375, 4.36 and 4,35. Example E 8 Printed and synthesized Ncc_ [4- (1-sulfur- Southern galactosyl) pent-2-yl] glycinate to prepare the title compound according to steps D, VII and M above, using pent-3-enen-2-one as the electrophile, and glycine third, butadiene The ester is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 3 3 8.3 9; M (measured 値): 363.9 (M + Na +). The selected nmr data is as follows: h-nmr -85- ___ This paper is of suitable size. It uses the Chinese National Standard (CNS) A4 specification (2iOX 297) and employees of the Central Bureau of Standards of the Ministry of Economic Affairs. Cooperating with Fei Du printed L 6 7 9 1 7 Α7 Β7 V. Description of the invention (83) (CD3OD): δ 4.43, 4.42, 4.37 (H-1) and 4.36. Example E 9 Synthesis of Νοι- [4,4 -2 Methyl-3-(1-thio-β-D-p-galactopyranosyl) cyclohex-1-yl] glycinate The title compound was prepared according to steps D, VII and M above, using 4,4-di Methylcyclohex-2-en-1-one is an electrophilic agent and a third glycine, and butyl ester is an amino ester. The mass spectrum data are as follows: M (estimated 値): 379.47; M (measured 値): 3 80.6 (Μ + Η +). The selected nmr data is as follows: 1H-ninr (CD3OD): δ 4.38 (Η · 1), 4.36, 4.34, and 4.31. Example E 1 0 Synthesis of Not- [3- (l -sulfur -β-D-p-galactopyranosyl) cyclohex-1-yl] glycine The title compound was prepared according to steps D, VII and M above, using cyclohex-2-en-1-one as the electrophile , And glycine is the third, butyl ester is an amino ester. The mass spectrum data is as follows: M (estimated 3): 3 5 1.42; M (found 値): 377.1 (M + Na +). The nmr data selected is as follows : 1H-nmr (CD3OD): S4.46 (H-1), 4.44, 4.40 & 4.36. Example E 1 1 Synthesis of Nα- [5- (1-thio-β-D-galactopyranosyl) -2,2-dimethylcyclohex-1-yl] glycine according to step D above, The title compound was prepared at M and M, using 6,6-dimethyl hexam-2-en-1-one as the electrophile, and the third glycine and the butyl ester as the amino ester. Example F 1 -86-This paper size applies the Chinese National Standard (CNS) A4 Regulations (210X297mm) (Please read the note on the back before filling this page)

, -Industrial Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs of the People's Republic of China, 467 9 1 7 A7 —___ B7 V. Description of the invention (84) Synthesis of Νβ- [2- (1-thio-β-D-galactopyranosyl) cyclopentyl -1-yl] -β · alanine according to steps D, VII and M above to prepare the title compound, using 2-aerocycline-1-one as the electrophile 'and β-alanine as the third, butyl Urethane. The mass spectrum data are as follows: M (estimated 値): 3 5 1.42; M (measured 値): 372_9 (M + Na +). The selected nmr data is as follows: iH_nmr (CD3OD): δ 4.54 (H-1), 4.52, 4.36 and 4.35. Example F 2 Synthesis of N β-[2-(1-thio-β-D-galactopyranosylpyrene) cyclohex-1-yl] · β · alanine according to steps D, VII and M above to prepare the title compound, And 2-air cyclohexyl-I-one is used as the electrophile 'and β-alanine is the third, butanine is the amino acid vinegar. The mass spectrum data are as follows: M (estimated 値): 3 6 5 · 4 5; M (measured 値) · 367.4 (M + H +), 389.9 (M + Na +), 412.0 (M + K +). The selected <nmr data is as follows: h-nmr (CD3OD): δ 4_47 (47-1), 4.42, 4.41, and 4.33 ° Example F 3 Synthesis of Nβ- [4 · phenyl-4- (1_sulfur-β- D · galactopyranosyl) but-2-yl] -β-alanine according to steps D, VII and M above to prepare the title compound, and 4-phenylbutan-3-en-2-one as electrophile Agent, and β-alanine third, and butyl ester is an amino acid ester. Mass spectrum data are as follows: M (estimated 値): 415.50; M (found 値): 417.0 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): S4, 28 (H-1), 4.17, 4.97 &amp; 3.96. ___- 87- This paper size is suitable for close home samples i CNS) A4 size (21GX297 male f) ~ ~~ (Please read the precautions on the back before filling this page)

467917 Printed by A7 B7, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the Invention (85) • Example F4 Synthesis of Ν β-[3-((1 -thio-β-D -galactopyranosyl) methyl) Ortho-2-yl] -β-alanine according to steps D, VII and M above to prepare the title compound, using 3-methylene-2-n-pentanone as the electrophile, and β-alanine Third, butyl ester is an amino ester. The mass spectrum data are as follows: 111-111111 '(€ 0300): 8 4.40 (11_1), 4, 37, 4.34, and 4.33. Example F5 Synthesis of N β-[3-(1 -thio-β · D -pyran'galactosyl) cycloheptan-1-yl] -β · alanine according to steps D, VII and M above to prepare the title compound, Cyclohept-2-en-1-one is used as the electrophile, and β-alanine is the third, and butyl ester is the amino ester. The mass spectrum data are as follows: M (estimated 値): 3 7 9 · 4 5; Μ (measured 値): 381.7 (M + H +), 403.5 (M + Na +), 426.0 (M + K +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4.46 (Η-1) and 4.3 8 Example F 6 Synthesis of N β-[4,4-dimethyl-3-(1 -sulfur- β-D-galactopyranosyl) cyclopentyl_1-yl] _β-alanine according to steps D, VII and M above to prepare the title compound, using 4,4-dimethylcyclofluorene-2-cotton'- 1-rim is an electrophilic agent, and β-alanine is third, butanine is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 379.44; M (found 値): 3 83.2 (M + Η +). The selected nmr data is as follows * W-nmr (CD3OD): δ 4.34 (Η-1), 4,33, 4.315, and -88-This paper is scaled to Zhong Jia Guan (CNS) Α size (210x197 cm) ) One (Please read the notes on the back before filling this page)

467917 Printed by A7 _ ^ ___ B7 ^ __ of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (86) 4.310 〇 Example F 7 Synthesis of Νβ · [3- (1-thio-β-D p ) Cyclopent-1-yl] -β-alanine according to steps D, VII and M above to prepare the title compound, using cyclopenta-2-en-1-one as the electrophile, and β-alanine third, Butyl esters are made from amino acids. Mass spectrum data are as follows: M (estimated 値): 3 5 1.42; M (found 値): 3 75.1 (M + Na +). The selected nmr data is as follows: lH_nmr (CD3OD): δ 4.41 (H-1) and 4.40. Example F 8 Synthesis of N β-[4-(1-thio-β-D-galactopyranosyl) pent-2-yl] -β-alanine according to steps D, VII and M above to prepare the title compound, using Pentamidine-2.-one is an electrophile, and β-alanine is the third, and butyl ester is an amino ester. The qualitative data are as follows: M (estimated 値): 3 52.42; M (measured 値): 356.0 (M + Η +). The selected nmr data is as follows: iH-ninr (CD3OD): 3 4.49 (H-1), 4.440 &amp; 4.43 5. Example F 9 Synthesis of Nβ- [4,4-dimethyl-3- (1-thio-β-D-galactopyranosyl) -cyclohex-1-yl] -β-alanine according to step D above , Η and M to prepare the title compound, using 4,4-dimethylcyclohex-2-en-1-one as the electrophile, and β-alanine third, and butyl ester as the release ester. Mass spectrum data are as follows: M (estimated 値): 393.50; M (measured 値): 3 99,3 (M + H +), 4 1 9.5 (M + N a +), -89- (谙 Please read the note on the back first Please fill in this page again for the contents] Binding paper ^ The size is applicable to the China Standard (CNS) A4 specification &lt; 210X297 mm) ~ 4 Printed by the Central Laboratories of the Ministry of Economic Affairs and Consumer Cooperatives 6 7 9 1 7 A7 _B7 V. Description of the invention (87) 44i.4 (M + K +). The selected nmr data is as follows: j-nmr (CD3OD): 5 4.35 (H-1), 4.34 &amp; 4.32. Example F 1 0 Synthesis of Νβ · [3- (1-thio-β-D-ii galactopyranosyl) oxan-1-yl] -β-diamine acid according to steps D, VII and M above to prepare the title The compound uses cyclohexan-2-one-1-one as an electrophile 'and β-alanine third, and butyl ester is an amino acid ester. Mass spectrum data are as follows: M (estimated 値): 3 6 5 · 4 5; M (measured 値): 367_0 (M + H +), 3 89.9 (M + Na +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4.46 (H-1), 4.44, 4.43, and 4.36 〇 Example F 1 1 Synthesis of Νβ- [5- (1-thio-β-D · pbiran Galactosyl) -2,2-dimethylcyclohex-1-yl] -β-alanine according to steps D, VII and M above to prepare the title compound, using 6,6-dimethylcyclohex-2- En-1-one is an electrophilic agent, and β-alanine is the third, and butyl ester is an amino ester. '' Example G 1 Synthesis of Nα- [2- (1-thio-β-D-galactopyranosyl) cyclopent-1-yl] -L-leucine according to steps D, VII and M to prepare the title compound, using 2-Gacyclopentane-1-one is an electrophilic agent, and L-leucine is third, and butyl ester is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 3 93.50; M (measured 値): 3 96.4 (M + Η +). The selected nmr data is as follows: lH-nmr -90- This paper size is applicable to China National Standard (CMS) 8 4 specifications (210X 297 mm) ----------- {Read the note on the back first Master again fill in this page} Order _-Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 467 917 'Λ7 Λ7 _ Β7 V. Description of Invention (88) (CD30D): δ 4,47 (H-1), 4.43 , 4_36 and 4.34. Example G2 Synthesis of Noc- [2- (l-thio-β_D-f galactopyranosyl) cyclohexyl-l-yl] -L-leucine according to steps D, VII and M above to prepare the title compound, 2-Gascyclohex-1-one is used as the electrophile, and L-leucine is the third, and butyl ester is the amino acid vinegar. Mass spectrum data are as follows: M (estimated 値): 407.53; M (found 値): 410.9 (M + Η +), 435.5 (M + Na +). The selected nmr data are as follows: iH-nmr (CD3OD): δ 4.49 (Η-1), 4.44, 4.41 and 4.37. Example G3 Synthesis of N a-[4-benzyl-4-(1-thio-β-D-galactopyranosyl) but-2-yl] -L-leucine according to steps D, VII and M above The title compound was prepared using 4-phenylbut-3-en-2-one as the electrophile and L-leucine as the third and butyl ester as the amino ester. Mass spectrum data are as follows: M (estimated 値): 4 5 8. 5 9; M (found 値): 480.5 (M + Na +). The selected nmr data is as follows: h-nmr (CD3OD): δ 4.39 (H-1), 4.36, 4.29, and 4.21. Example G5 Synthesis of Not- [l- (l-thio · β-D-p galactopyranosyl) cyclohept-3-yl] -L-leucine according to steps D, IX and M above, to prepare the title compound, Cyclohept-2-en-1-one is used as the electrophile, and L-leucine is the third, and butyl ester is the amino ester. The mass spectrum data are as follows: M (estimated): 4 2 1 · 5 5; M (actually measured): -91-This paper size applies to China National Standard (CNS) A4 (210 × 297 mm) (read the first Please fill in this page for the note items]-Order

IV 679 17 25. Description of the invention (89) 421_7 (M + H +), 448.0 (M + Na +). The selected nmr data is T: 1H-ninr (CD3OD): S4.44 (H-1), 4.43 &amp; 4.36. Example G6 Synthesis of Nα- [4,4-Difluorenyl 3- (1-thio-β-D-galactopyranosyl) -cyclopent-1-yl] -L-leucine according to step D above, The title compound was prepared from VII and M, using 4,4-dimethylcyclopent-2-en-1-one as the electrophile, and L-leucine as the third, and butyl ester as the amino ester. The mass spectrum data are as follows: M (estimated 値): 42 1.55; M (found 値): 422.3 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4.320 (Η · 1) and 4.315. Example G 7 Printed by the Shellfish Consumer Cooperative of the Central Biaofeng Bureau of the Ministry of Economic Affairs (谙 Please read the notes on the back before filling this page) Synthesis of Ν α-[3-(1 -thio-β-D -galactopyranosyl) Cyclopent-1-yl] -L-leucine According to steps D, VII and M above, the title compound was prepared, with cyclopent-2-en-1-one as the electrophile, and L. leucine Third, butyl ester is an amino ester. The mass spectrum data are as follows: M (estimated 値): 3 93.50; M (found 値): 393_.6 (M + H +), 417.0 (M + Na +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4'3 80 (H-1), 4,375, 4.370 and (367 ° Example G 8 Synthesis of Nα- [4- (1-thio-β-D- Galactopyranosyl) pent-2-yl] -L-leucine according to steps D, VII and M above to prepare the title compound, and using pent-3-fluoren-2-yl as an electrophile, and L- The third is leucine, and the butyl ester is urethane. -92- The paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 male f) A7 B7 46 7 9 1 V. Description of the invention (90) The data is as follows: M (estimated 値): 3 9 5.5 9; M (actually measured 値): --------- i II-·-. (\ (谙 Please read the notes on the backside first, then fill out this Page) 3 96.8 (M + H +), 419.1 (M + Na +) and 440.9 (M + K +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4_42 (H-1), 4.41 , 4.405 and 4.40. Example G9 Synthesis of Nα- [4,4-dimethyl-3- (1-thio-β-D-galactopyranosyl) -cyclohex-1-yl] -L-leucine Prepare the title compound according to steps D, VII and M above, using 4,4-dimethylcyclohexane-2 -fluoren-1-one as the electrophile, and L-leucine third and butyl ester as the amine Esters.Mass data It is as follows: M (estimated ：): 436,58; M (measured 値): 43 8.0 (M + H +), 461.4 (M + Na +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4.38 (Η-1) and 4.34. Example G 1 0 Printed and synthesized Να- [3- (1-thio-β-Di »taste galactosyl) cyclohex-1 by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. -Yl] -L-leucine according to steps D, VII and M above to prepare the title compound, and cyclohex-2-en-1-one as an electrophile, and L-leucine tertiary, butyl ester Is an amino acid ester. The mass spectrum data is as follows: M (estimated 値): 40.753; M (measured 値): 408.4 (M + Η +). The selected nmr data is as follows: 1H-nmr (CD3OD) : δ 4.46 (H-1), 4.42, 4.40 and 4.33. Example Η 1 Synthesis &quot; N (λ- [2- (1-thio · β · D -ρ galactopyranosyl) cyclopent-1-yl ] -L-Histidine-93- This paper size is in accordance with Chinese National Standard (CNS) Λ4 specification (2! 0 X 297 mm) 4 6 7 9 1 7 Printed by ABC Consumers Cooperative of Central Standards Bureau of Ministry of Economic Affairs A7 ____B7 V. Description of the invention (91) Prepare the title compound according to steps D, IX and N above, and use 2-aircyclopentan-1-one as a parent Sub-agents, and L- amino acid ester is methyl histamine. Mass spectral data are as follows: M (estimated 値): 4 1 7.48; Μ (measured 値): 4 1 8 · 7 (M + Η +). The selected nmr data is as follows: h-nmr (CD3OD): 8 4.45 (11-1), 4.41'4.40 and 4.29. Example Η 2 Synthesis of Ν α-[2 · (1-thio-β -D -galactopyranosyl) cyclohex-1-yl] -L-histidine according to steps D, Η and Ν above to prepare the title compound With 2-chlorocyclohexan-1-one as the electrophile and L-histidine sulfonate as the amino ester, the mass spectrum data are as follows: M (estimated 値): 4 3 1.50; Μ (measured 値); 433 · 6 (Μ + Η +). The selected nmr data is as follows: iji-nmr (C 9 3 0 D): δ 4.5 2 (Η 1), 4.4 5, 4 · 4 0 and 4.2 8. Example Η 3 Synthesis of Nα- [4-phenyl-4- (1_thio-0_〇 · »pyranosyl) butan-2-yl] -L-histidine is prepared according to steps D, D and Ν The title compound, with 4-phenylbutane-3_fluoren-2-one as the electrophile 'and L-histidine methyl acetate as the amino acid ester. Mass spectral data are as follows: M (estimated 値): 481.56; M (measured 値): 482.8 (M + Η +). The selected nmr data are as follows: iH-nmr (CD3OD;): 3 4.38 (11-1), 4.36, 4.23 and 4.16. • Example Η 5 Synthesis of Να- [3- (1-thio-β-Di »galactopyranosyl) cycloheptan-1-yl] _L-histidine-94-ft scale applicable to the Chinese Standard (CNS) (21GX297) ((Please read the precautions on the back before filling this page)

4 6 7 9 17 A7 B7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China. 5. Description of the Invention (92 The title compound was prepared according to steps D, Η and N, and cyclohept-2-en-1 · one was used as the electrophile. And L-histidine methyl ester are amino esters. The mass spectrum data are as follows: M (estimated 値): 445.54; M (measured 値): 448.0 (M + Η +). The nmr data selected is as follows: iH- nmr (CD3OD): δ 4.50 (Η-1), 4.44, 4'41, and 4.32. Example Ιί Synthesis of Να- [4,4-dimethyl-3- (1-thio-β-D-pyran Galactosyl) -cyclopent-1-yl] -L · histidine according to steps D, 化合物 and N above to prepare the title compound, using 4,4-dimethylcyclopentan-2- 晞 _1_one as The electrophile and L-histidine methyl ester are amino esters. The mass spectrum data are as follows: M (estimated 値): 445.54; M (measured 値): 447.6 (M + Η +). Nmr selected The data are as follows: -nmr (CD3OD): δ 4 · 33 (Η-1), 4.32, 4.305, and 4.30. Example Η 7 Synthesis of N &quot; tx_ [3- (1-thio · β-D-ρ galactopyranosyl) ) Cyclopent-1-yl] -L_histidine according to steps D, IX and N above to prepare the title compound, using cyclopenten-1-one as the electrophile , And L-histidine methyl ester is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 418.48; M (found 値): 418. (M + Η +). The nmr data selected is as follows: iH -nmr (CD3OD): 3 4.39 (11_1), 4.38, 4.36 and 4'32. Example Η 8 Synthesis of Nα- [4- (1-thio-p-Dp galactopyranosyl) pent-2-yl]- L · Histamine 95 private paper size applies Chinese National Standard (CNS) A4 specification (210X297 male f) (谙 Please read the note on the back before filling this page) Order by the Central Bureau of Standards of the Ministry of Economic Affairs ΗPrinted by Consumer Cooperatives 4 6 7 9 1 7 Α7 ---- B7 V. Description of the invention (93) Prepare the title compound according to steps D '' and N above, and use pent-3-enone as electrophile and L-histidine The methyl ester is an amino acid ester. The mass spectrum data is as follows: M (estimated 値): 4 1 9 · 4 9; M (measured 値): 42 0 2 (Μ + Η +). The nmr data selected is as follows: iH- nmr (CD3OD): δ 4.44 (H-1), 4.41, 4,40, and 4'36. Example Ή 9 Synthesis of Nα- [4,4-dimethyl- 3- (1-thio-β-Dp ratio) Galactosyl) -cyclohex-1-yl] -L-histidine according to steps d, d and n above to prepare the title compound. 4,4-dimethyl-cyclohex-l-one -2_ Xi is an electrophile and L - Histamine amine from ethyl acetate. Mass spectrum data are as follows: M (estimated 値): 459.56; M (found 値): 462.2 (M + Η +). The selected nmr data is as follows: 1H-nmr (CD3〇D): δ 4.364 (Η-1), 4.3 5 7 and 4.34. Example Η 1 0 Synthesis of Ν &quot; (χ · [3- (1- -thio-β-D _ &lt; * biran. Galactosyl) cyclohex-1-yl] -L-histidine according to step D above , 化合物 and Ν to prepare the title compound, with cyclohex-2-ene-1_rim as the electrophile, and L-histidine methyl ester as the amino acid ester. Mass spectrum data are as follows: M (estimated 値): 4 3 1. 5 1; M (measured 値): 4 3 3.2 (M + Η +). The selected nmr data is as follows: (CD3OD): 5 4.43 (11-1), 4.425, 4.39, and 4.35. Example 11 Synthesis Να- [2- (1-thio-β-D-galactopyranosyl) cyclopent-1-yl] -L-tryptophan _____- 96- This paper size applies to China National Standard (CNS) Α4 specifications (210 × 297 公 楚 1 ~ ------------j-. .. {#First read the precautions on the back before filling in this purchase) -Order-

Ur 467 9 1 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (94) Prepare the title compound according to steps D, Η and N above, using 2-chlorocyclopentan-1-one as the electrophile , And L-tryptophan sulfonate is an amino ester β. Mass spectrum data are as follows: M (estimated 値): 466.55; M (found 値): 467.5 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): 8 4.51 (11-1), 4_39, 4.28 and 4.27. Example 12 Synthesis of Na-[2-(1 -thio-β -D -I »galactopyranosyl) cyclohex-1-yl] -L-tryptophan The title was prepared according to steps D, IX and N above. The compound uses 2-cyclohexyl-1-fluorene as the electrophile and L-tryptophan methyl ester as the amino acid ester. Mass spectral data are as follows: M (estimated 値): 480.59; M (found 値): 481.9 (M + H +), 505.3 (M + Na +). The selected nmr data is as follows: j-nmr (CD3〇D): δ 4.4 6 (Η · 1), 4.40, 4.24, and 4 _ 0 9 0 Example 13 Synthesis of Not- [4-phenyl- 4- (1 -Sulfur-galactopyranosyl) but-2-yl] -tryptophanic acid according to the above steps 骒 D, Η and N to prepare the title compound, using 4-phenylbutan-3-en-2-one as the parent Electron agents, and L-tryptophan methyl ester are amino esters. Mass spectrum data are as follows: M (estimated 値): 5 3 1 64; M (found 値): 531.3 (M + H +). The selected nmr data is as follows: A-ηιηΓ (C D 3 Ο D): δ 4.2 4 (Η-1), 4.2 3, 4 1 4 and 4.0 9. Example I 5 Synthesis of Nα- [3- (l-sulfur-βD-p ratio-97-)-This paper size is applicable to China National Standard (CNS) A4 specifications (210X297). (#Read the precautions on the back first This education), 1T 4 6 7 9 1 7 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (95) Galactosyl) cycloheptan-1-yl] -L-tryptophan In step D, hydrazone and N, the title compound is prepared using cyclohept-2-en-1-one as the electrophile and L-tryptophan methyl ester as the amino acid ester. Mass spectral data are as follows: M (estimated 値): 494.60; M (found 値): 495.9 (M + Η +). The selected nmr data is as follows: ^ -nmr (CD3OD): δ 4.50 (Η-1), 4.44, 4.41, and 4.32. Example 16 Synthesis of N a-[4,4-dimethyl-3-(1-thio-β-D-galactopyranosyl) -cyclopent-1-yl] -L-tryptophan according to the steps above D, H and N prepared the title compound with 4,4-difluorenylcyclopent-2--2--1-one as the electrophile and L-tryptophan methyl ester as the amino acid ester. Mass spectrum data are as follows: M (estimated 値): 4 9 4.6 Ο; Μ (actually measured 値 495 · 6 (M + Η +). The selected nmr data is as follows: A-nmr (CD3OD): 3 4.26 (Hl) , 4.22, 4.20 &amp; 4.13e Example 17 Synthesis of N (χ · [3- (1-thio-β-D-p-galactopyranosyl) cyclopent-1-yl] -L-tryptophan according to step D The title compound was prepared using hydrazone and N, using cyclopentan-2-fluorenone-1 · one as an electrophile, and L-tryptophan methyl ester as an amino acid ester. Mass spectrum data are as follows: M (estimated): 466.5 5 M (measured 値): 467..9 (M + H +). The nmr data selected is as follows: [H-nmr (CD3〇D): 8 4.33 (11-1), 4.32, 4.30, and 4.23. Examples 18 Synthetic Ntx- [4- (l-sulfur-β-Dp ratio σ south _..... ___ -98- This paper size applies to China® Home Standard (CNS) Α4 specification (2! GX297 male f) one ( (Read the notes on the back before filling in this page)

Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs ______B7 V. Description of the Invention (96) &quot; Galactosyl) pent-2-yl] -L-tryptophan The title compound is prepared according to steps D, Η and N above Pent-3-en-2-one was used as the electrophile, and L-tryptophan methyl ester was used as the amino acid ester. The mass spectrum data are as follows: M (estimated 値): 4 6 8 ′ 5 7; M (measured 値): 4 9 0.9 (M + Na +). The selected nmr data is as follows: iji-nmr (CD3OD): 3 4.30 (H-1), 4.27, 4.22 &amp; 4.09. Example 19 Synthesis of Noc- [4,4-dimethyl-3- (1-thiopyranosyl) cyclohex-1-yl] -L-tryptophan The title was prepared according to steps D, IX and N above The compound uses 4,4-dimethylcyclohex-2-ene-1-rim as an electrophile, and L-tryptophan is used as the amino ester. The mass spectrum data are as follows: M (estimated 値): 508.63; M (found 値): 512.1 (M + Η +). The selected nmr data is as follows: j-nmr (CD3OD): δ 4.30 (H-1), 4.26 and 4,21. Example 11 0 Synthesis of N α-[3-(1-thio-β-D-galactopyranosyl) cyclohex-1-yl] -L-tryptophan according to steps D, VII and NH above to prepare the title Compound, and cyclohex-2-one-1-one as an electrophile, and L-tryptophan methyl ester as an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 4 0 0 ′ 5 9; M (measured 値): 4 8 3 · 9 (M + Η +). The selected nmr data is as follows: j-nmr (CD3OD): δ 4.36 (Η · 1), 4.35, 4.33 and 4.24. Example J1 Synthesis of TN (χ- [2- (1-sulfur-β-D-p than Ming-99-)-This paper size is applicable to China National Standard (CNS) A4 specification (210X297) 漦 (# 先 闻 读 NOTES on the back $ Item, please fill in this page) Order h—Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives. M B7 V. Description of the invention (97) ~~~~ ~. Galactosyl) cyclopentan-1-yl] -L- Arginine was prepared according to steps D, VII and 0 above, using 2-chlorocyclopentan-1-one as the electrophile, and L-arginine methyl ester as the amino acid ester. The mass spectrum data is as follows: M (Estimated 値): 43 6.52; M (measured 値): 43 6.2 (M + Η +). The selected nmr data is as follows: iH_nmr (CD3〇d): δ 4.54 (Η-1), 4.43, 4.41 And 4'28 〇 Example J2 Synthesis of N α-[2-(1 -sulfur β β d-n biran, galactosyl) cyclohex-1-yl] -L-arginine framed step D above, The title compound was prepared using amidine and O, using 2-chlorocyclohexan-1-one as the electrophile, and L-arginine methyl ester as the amino acid ester. Mass spectrum data are as follows: M (estimated): 4 5 0.5 6 Μ (Measured 値): 4 5 3.5 (Μ + Η +). The selected nmr data is as follows: iH-nmr (CDj OD): δ 4.47 (Η-1), 4.45, 4.44 and 4.38 0 Example J3 Synthesis of Νοι-[4-benzyl-4-(1-sulfur-β-D-p-galactopyranosyl) butan-2 -Yl] -L-arginine acid Steps D, H and O above were used to prepare the title compound, using 2-gascyclohexan-1-one as the electrophile, and L-arginine methyl ester as the amino acid The mass spectrum data of Ester >> are as follows: M (estimated 値): 5 01.62; M (measured 値): 503.8 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): S4.32 (H-1 ), 4,31 &amp; 4.30. Example J 5 Synthesis of Ntx- [3- (l-sulfur-β-D-pyran-100)-This paper is suitable for the standard of China, (CNS) A4 (210X297 mm) ) (Read the precautions on the back and fill out this page)

Printed by A7 ___B7 of the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (98) Galactosyl) cycloheptan-1-yl] -L-arginine according to steps D, Η and 0 above to prepare the title compound Cycloheptan-2- 晞 -1-week was used as the electrophile, and L-arginine methyl ester was the amino acid ester. Mass spectral data are as follows: M (estimated 値): 464.58; M (found 实): 467.1 (M + Η +). The selected nmr data is as follows: W-nmr (CD3OD): δ 4.48 (Η-1), 4.46 and 4.43 ° Example J6 Synthesis of Nα- [4,4 -dimethyl-3- (1-thio · β · ϋ) -&lt; »galactopyranosyl) -cyclopent-1-yl] -L-arginine according to steps D, IX and 0 above to prepare the title compound using 4,4-dimethylcyclopentan-2- Enen-1-one is an electrophile, and L-arginine methyl ester is an amino acid ester. Mass spectrum data are as follows: M (estimated 値): 4 6 4.5 8; Μ (found 値): 465.6 (M + Η +). The selected nmr data is as follows: W-nmr (CD3OD): 3 4.37 (H)), 4.35, 4.34 & 4.30. Example J7 Synthesis of 1 ^ 〇1- [3- (1-thio-β-D-p-galactopyranosyl) cyclopent-1-ylb L-arginine according to steps D, Η and 0 above to prepare the title The compound uses cyclopent-2-en-1-one as an electrophile and L-arginine methyl ester is an amino acid ester. Mass spectral data are as follows: M (estimated 値): 43 6.53; M (found 値): 437.69 (M + Η +). The selected nmr data is as follows: iH_nnir (CD3OD): 8 4.37 (11-1), 4.35 and 4.34. Example J 8 Synthesis of N &quot; tx- [4- (l -sulfur-β-D-&gt; * 比 南 _ ___-101-

This paper &amp; standard applies to China Touch Standard (CNS) 8-4 specifications (21 () χ297 公 楚 J --- II -----, .. (锖 Please read the precautions on the back before filling in this page) Order 4 6 7 9 A7 B7 V. Description of the invention (99) Galactosyl) pent-2-yl] -L-spermine acid The title compound was prepared according to steps D, Η and 0 above, with pent-3-enone as the parent. Electron agents, and L-arginine methyl ester are amino esters. Mass spectral data are as follows: M (estimated 値): 4 3 8 _ 5 4; Μ (measured 値): 4 3 7 _ 3 (Μ + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): δ 4..46 (Η-1), 4.4 1, 4.3 9 ^ 14.3 8 〇 Example J 9 Synthesis of Nα- [4,4-dimethyl-3 -(1-thio-β-Dp galactopyranosyl) cyclohex-1-yl] -L-arginine according to steps d, d, and 0 above to prepare the title compound, using 44 · dimethylcyclohexyl 2-en-1-one is an electrophile, and L-arginine methyl ester is an amino acid ester. The mass spectrum data are as follows: M (estimated 値): 478.6; M (found 値): 479.0 (M + Η +). The selected nmr data is as follows: iH_nmr (CD3OD): 6 4.43 (H-1), 4.41, 4.38 &amp; 4.32. '' Example J10 · Printed synthesis of Nα- [3- (1-thio-β-Dp galactopyranosyl) cyclohex-1-yl] -L-arginine by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs as above In step D, hydrazone and 0 are used to prepare the title compound, and cyclohex-2 · en-1-one is used as the electrophile 'and L-arginine methyl ester is used as the amino acid ester. Mass spectral data are as follows: M (estimated 値): 450.5 5; M (measured 値): 451 -8 (M + Η +). The selected nmr data is as follows: iH-nmr (CD3OD): 8 4.34 (11-1), 4_33, 4.32 and 4.29. _ Example 1 Synthesis of 2,2 monomethyl-4- (cyclobut-1-ylamino) pentan-1-yl ι — —102 — This paper is suitable for tils household materials (CNS) A view frame (210X297 (Mm) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 6 7 b 1 7 ('A7 t ____ B7 V. Description of the invention (100) Sulfur-β-D-galactopyranosyl Enantiomers This example illustrates the preparation of individual diastereoisomers of compounds of formula I. Step 8-Synthesis of (111,8) -2,2-dimethylcyclopentan-4-one-1- Radical 2,3,4,6 -methyl-0 -lauryl-1 -sulfur β -D -galactopyranosylpyrene: p-S -ethynyl-2,3,4,6-methyl- 〇-Lauryl-1-thio-0-〇-galactopyranosyl (5 g, 5 mmol) (from Example C above) and 4,4-dimethyl-2-cyclopenta-1 -Ketone (500 mg, 4.45 mmol) in anhydrous (: 112 (: 12 (1 () ml)), Et2NH (6 ml) was added under argon. After 3 hours, the mixture was concentrated and purified by column chromatography (Si02, pentane, EtOAc, 9: 1) to give the title compound as a mixture of diastereoisomers (3.54 g, 6 6%). Step B-Isolation of (lR, S) -2,2- Methylcyclopentane-4-rim-triphenyl-2,3,4,6-methyl-0-lauryl-1-thio-β-Dp galactose: y :: two non-pairs from step A Enantiomers (5 g, 4.8 mmol) were separated by column chromatography (Si02, pentane, EtOAc, 9: 1) to give (1S) -2,2-dimethylcyclopentane-4-fluorene-1 -Methyl-2,3,4,6 -Methyl-0-Lauryl-1 · Sulfur_β_〇_ Galactoaluminum (428.8 mg, 8%) and (lR) -2,2 · dimethyl Cyclopentyl-4-keto-1-yl 2,3,4,6-cyclo-0-lauroyl-1-thiofluorenyl_0_, galactopyranoside (373.8 mg, 6%), plus unresolved A mixture of compounds (2.74 g, 52%). Step C-Synthesis of (1S, 4RS)-and (1R, 4RS) -2,2-dimethyl-4_epicyclopent-1-yl 2,3, 4,6-Lauryl-1-thio-pyral galactose: diastereomeric stereoisomers purified from step B (in separate reaction flasks) (3 20 mg, 0-3 mmol) Moore) Yu Xan, Anhydrous Tetranitrogen ρ Loss 103 This paper size is applicable to Chinese National Standard (CNS) Α4 size (210 X 297 cm) (Please read the notes on the back first and fill in this K) ^ Bing 46 7 Central Ministry of Economic Affairs Printed by the Bureau of Standards and Consumers Cooperative A7 B7 V. Description Ming (101) (3 ml), methanol (0.5 ml) and isopropanol (2 ml) 'was added NaBH4 (0.12 mmol) under an argon atmosphere. After 30 minutes, AcOH (1 drop) was added and the mixture was concentrated. The residue was dissolved in MeOH (2 ml) and packed into a C18 silica column (5 g). The column was washed with MeOH (50 mL), and the product was dissolved in pentane (50 mL) to give (1S, 4RS) -2,2-dimethyl 4-hydroxycyclopent-1-yl 2,3,4 , 6 · -O-lauryl-1-thio-β-D-galactopyranoside (281 mg, 88%) and (lR, 4RS) -2,2-dimethyl-4-hydroxy · Cyclopentyl-1-yl 2,3,4,6 · Ci-0-0-lauroyl-1-thio-β-D-galactopyranosylhydrazone (297 mg, 93%) Step D-synthesis (1S, 4RS)-and (1R, 4RS) -2,2-dimethyl- 4-o-methanesulfonyloxycyclopent-1-yl 2,3,4,6-zan-0 -laurel Fluorenyl-1-thio-β-D-galactopyranosyl group: (1S, 4RS) and (1R, 4RS) mixture (in separate reaction flasks) from step C (280 mg, 0.3 mmol) Ear) In anhydrous tetrahydrofuran (2 ml) and anhydrous eridine (4 ml), under argon atmosphere, add methanesulfonium (0.5 ml). After 12 hours, the mixture was washed with 0.5 M H C1 and extracted with pentane. After concentration, the residue was purified on C18 silica (5 g) and, as described in Step C, (18 ', 4118) -2,2-dimethyl-4-0-methanesulfonyloxycyclopentane- 1-yl 2,3,4,6-H-lauryl-1-thio-0-〇-galactopyranosyl (281 mg, 88%) and (5) (lR, 4RS) -2 , 2-Dimethyl-4-0-methanesulfonyloxycyclopent-1-yl 2,3,4,6 -methyl-0-lauryl-1-thio-β-D-pyran Lactose tincture (297 mg, 93%), white solid particles after evaporation of pentane. Step E-Synthesis of (1S, 4R)-, (1S, 4S)-, (1R, 4S)-, and -104- This paper size applies the Chinese National Standard (CNS) Ad Specification (2H) X 297 male t &gt; ( #Read the notes on the back before filling this page)

&gt; 1T 4 6 7 9 17 A7 B7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (10.2) (1 玟, 4 feet) -2,2-dimethyl-4-azide ring Amyl-1-yl 2,3,4,6-cyclo-o-lauroyl-1-yl-thio-β-D-galactopyranosylpyrene ... (1S, 4RS) and (1R, 4RS) are from The mixture from step D (in separate reaction flasks) (250 mg, 0.2 mmol) was added to anhydrous DMF (8 ml) and anhydrous THf (3 ml). NaN3 (340 mg, 5 mmol) and 18-crown-6 (180 mg). After 2 hours, the mixture was concentrated and purified on C18-silica (5 g) as described in step c. Rechromatography (SiO2, pentane / EtOAc, 9: 1) can separate the diastereoisomeric compounds, resulting in a pure (18,41〇-2,2-diamidino-4-azido ring Pentamyl-1.yl 2.3.4.6-methyl--0-laurinyl-1-thio-0-〇-1 «is even more galactose (63 mg, 65%); (lS, 4S) -2,2- Dimethyl-4-azidocyclopentane-1.yl 2.3.4.6- bis-〇-lauroyl-1-thio-0-〇- »» galactoprant (29 mg, 9%) '' (LR, 4S) -2,2-Dimethyl-4-azidocyclopentan-1-yl 2.3.4.6- bis-0-lauroyl-1-thio-β-Dp galactopyranoside (68 mg, 28%); and (1R, 4R) -2,2-dimethyl-4-azidocyclopent-1-yl-2,3,4,6 -methyl-o-lauroyl- 1-Sulfur-β-D-galactopyranosyl pyrene (21 mg, 9%) Step F-Synthesis of (1S, 4R)-, (1S, 4S)-, (1R, 4S)-and (1R, 4R ) -2,2-dimethyl-4-aminocyclopentyl-i-yl 2,34,6-methyl- 0-lauroyl-1-thio-β-D-pyridinogalactoside: from E 2,2-dimethyl-4-azido-cyclofluoren-1-yl 1-sulfur_0_ £) _galactopyranoside ^ 4 diastereoisomeric isomers (5 mg, 15 μmol) in anhydrous isopropanol (1 ml) and anhydrous B (1 mL) under an argon atmosphere, was added NaBH ^ lS micromolar) and NiChpo micromolar). After i hours, the mixed -105- Thai paper size is applicable to the Chinese National Standard (CNS) A4 gauge (21 0 X 297 mm) (谙 Please read the note on the back side and fill in this page;}

Printed by the Central Standards Bureau, Ministry of Economic Affairs, Masonry Consumer Cooperatives 4 6 7 9 1 a? B7 V. Description of the Invention (1 03) * The product was neutralized with AcOH (1 drop), concentrated and purified on C18-silica (2 g ) As described in step C, (1S, 4R)-, (1S, 4S)-, (1R, 4S)-and (lR, 4R) -2,2-dimethyl-4-aminocyclopentane -Kibuthione-β-D. Galactopyranoside (5 mg each; quantitative). Steps to synthesize (1S, 4R)-, (1S, 4S) ·, (1R, 4S)-and (111,411) -2,2-dimethyl-4- (cyclobut-1-ylamino) cyclopentyl- 1-yl 2,3,4,6 -Di-O-lauroyl-1-sulfanyl-β-D-galactopyranosylpyrene; Source 1} Step F2,2-dimethyl-4-amino -Cyclopyridine-1-yl 1-thio-β-D-galactopyranosylpyrene, each of the 4 diastereoisomeric forms (in each reaction flask) (2 mg, 6.8 μmol) in anhydrous methanol (1 ml) and anhydrous dichloromethane (1 ml), cyclobutanone (250 µl, 3.4 mmol) and sodium triacetoxyborohydride (10 mg, 47 µmol) were added under an argon atmosphere. ). After 24-48 hours, toluene (1 ml) was added, and the mixture was concentrated. The residue was purified on C18-silica, as described in step C, yielding 2.1-2.4 mg (quantitative) of each: (18.411) -2,2 -Dimethyl-4- (cyclobut-1-ylamino) cyclopent-1-yl1-thio-PD-galactopyranoside (B6HA); M (estimated): 3 6 1.50; M ( Found 値): 361.6 (M + H +); 1H-nmr (CD3OH) · δ 4.292 (Η-1); (18.411) -2,2-dimethyl-4- (cyclobut-1-ylamino) ) Cyclopent-1-yl 1-thio-β-D-galactopyranosyl pyrene (B6ΗΑ); M (estimated 値): 3 61.50; M (measured 値): 361.6 (M + H +); W-nmi ^ CDsOH): δ 4.3 1 5 (Η-1); (1 foot, 48) -2,2-dimethyl-4- (cyclobut-1-ylamino) cyclopent-1-yl 1-- 106- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Read the first note on the back 邛 #Fill this page), ιτ 6 9 Γ: A? __B7 V. Description of the invention (1〇4 ) Sulfur-β-D-galactopyranosyl pyrene (B6HA); M (estimated radon): 361.50; M (measured radon): 36i.6 (M + H +); W-nmi ^ CDsOH): δ 4.300 ( Η-1); (1R, 4R) _2,2 · dimethyl-4- (cyclobut-1-ylamino) cyclopent-1- 1-sulfur-β-D-galactopyranosyl pyrene (B6HA); M (estimated): 3 61.50; M (measured): 361.6 (M + H +); JH- nmr (CD3OH): δ 4.290 ( H-1). Example 2 Adhesion of [3- (carboxyamidoamino) -n-fluoren-2-yl] methyl 1-thio-β-D-galactopyranosylpyrene to a solid support ) N-Fuk-2-yl] methyl 1-sulfuryl-β-D-galactopyranoside (2.1 g, 4.5 μmol, from Example D4 above), Chromosorb P (449 Mg, prepared as described in U.S. Patent No. 4,137,4011Q and Westal et al. 11), and hydroxybenzotriazole (1-3 mg, 9.4 micromolar) in DMF (1 ml, 4A molecular sieve Dry on top) and add diisopropylcarbodiimide (1.4 μl, 9.0 μmol). After 75 hours the beads were filtered off and washed with water, DMF, MeOH and CH2C12. For the beads formed in MeOH (1.5 ml), add liver vinegar (0.5 ml). After 16 · 5 hours, the beads are filtered and washed with water, DMF, MeOH, CH2C12 and pentane. The beads were suspended in MeOH and the supernatant was decanted repeatedly to remove finely divided particles. Drying under high airspace yields 433 mg of the product, of which [3- (carboxyamidoamino) -n-syl-2-methyl] methyl 1-thiogalactopyranoside is very covalently attached to Chromasorb P, which is based on Chorarasorb P Amine and 1-sulfur galacto-107- This paper size is applicable to Chinese National Standard (CNS) A4 specification (2 丨 0X297). ^^--p-(谙 Please read the precautions on the back before filling this page )

, 1T Printed by the Central Standards Consumers Cooperative of the Ministry of Economic Affairs 4 6 7 9] ΑΊ B7

Chromosorfa pj 5. The description of Fat Hu (amidine chain is formed between the rebel groups of the sugar derivative No. 10, as shown in the following formula π. The phenol / H2S04 analysis method by M. Dubois et a1.9 shows that there are 4 〇Micromole / gram included in the yield. Guarantine first read the precautions of back 1¾ before

i Example 3 Solid phase synthesis of 1-thiogalactose This example illustrates the solid phase synthesis of a 1-thiogalactose derivative of formula I. Step A- Synthesis of 1-dithioethyl · 2,3,4,6-,-〇 · ethylfluorenyl-galactopyranophene: 1-thio-2,3,4,6- 肆 -0-ethyl Fluorenyl-P galactopyranosyl: y: (500 mg, 1.37 mmol) and N-ethyl-sulfenylfluorenyldicarboxylic acid diethyl «(360. gram '2.0 mmol Ear) (prepared as described by T. Mukaiyama 12) Dissolved in Diqijiawan (14 ml), and stirred away at room temperature. After 10 minutes, the solution was concentrated and subjected to column chromatography (Si02, hexane, ethyl acetate 2: 1) to produce 1-dithioethyl-2,3,4,6-ethyl-0 ethyl alcohol- R-galactopyranoside (580 mg, quantitative) appeared as a white solid (Rf 0.27 in hexane / ethyl acetate (2: 1)). ΐ-NMβ (360 MHz, CHCI3): δ 1.30 (dd, 3 Η, J = 7.4 Hz, CH3), 1.96, 2.02, 2.03, 2.13 (4 s, 12 H, 4 CH3CO), 2.79 (ddd, 2 H , J = 7.4 Hz, J = 7.4 Hz, J = 1.3 Hz, CH ^, 3.94 (ddd, 1 H, = 1.0 Hz, JSM = 6.6 Hz, J3, 6b = 7.6 Hz, 5-H), 4.10 (ddd , 108- This paper size applies to China's National Standards (CNS) A4 specification (210X297 mm). Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 4 6 7 9 1 A7 B7 V. Description of the invention (106) 2 H, 61 -Ht 6b-H), 4.51 (d, 1 H, J, .2 = l〇.〇Ηζ &gt; 1-H), 5.05 (dd, 1 H, J2J «l〇.〇

Hz, J34 = 3.3 Hz &gt; 3-H)), 5.38 (dd, IH, J12 = i〇.〇Hz, J3, 3 = l〇.〇Hz, 2-H), 5.40 (dd, 1 H &gt; JM -3.3 Hz, ke! · 〇Hz, 4-H); m / z Ca | ^ rifir Cl (iHM〇9S3 (M + Na) 447.1, measured 彳 # 7.0. -Λ · Step B-Synthesis 1- Dithioethyl-p.D-galactopyranoside: 1-dithioethyl 2,3,4,6-cyclo-lauroyl-P galactose from step A (500 mg (1.18 mmol), dissolved in anhydrous methanol (10 ml) and treated with methanolic sodium methyloxide (1 M, 150 μl). After 2 hours, the solution was treated with Amberlite '1R-120 resin (-+) Neutralization, filtration and concentration can produce 1-dithioethyl-6-p-D-galactopyranosylpyrene as a white solid (300 mg, quantitative). Step C-1 -dithioethyl-6 -β-D -galactopyranosyl ^: Coupling to resin: 1-dithioethyl-6- p- D-»« galactopyranosamidine (200 mg, 780 micromolar) is dissolved in anhydrous pyridine (8 ml). Add trityl gas-resin (] | Yin Li, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs, {Note on the back of the dish, please pay attention to this page) gram, 4 5 0 micromo ear Diphenyl. Methyl gas resin, 0.95 millimoles / g of activated gas were added, polymer matrix: copolystyrene_1% DVB, 200-400 mesh sieve, Novabiocliem) and DMAP (5 mg), and the mixture was in The resin was filtered under heating at 60χ for 2 hours and 4 hours, and then washed with methanol, tetrazine, dichloromethane, and diethyl ether (10 ml each) to produce 1_dithioethyl_0_D ρ ratio. Galanose: y: Covalently linked to the trityl resin via the 6-position obtained group 'Step D-Production of free state thiols on the resin: The resin (50 mg) from step c Anhydrous tetrahydrofuran (15 ml) e was added with anhydrous methanol (300 microliters) 'dithioisoerythritol (74 mg) and triethylamine (18 micro ___- 109- CNS) A4 specification (210X297 Gongchu) Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China Yin Fan 16 7 9] 7 A1 B7 5. Description of the invention (107) 1 liter), and the mixture was shaken at room temperature for 10 hours. The resin was filtered off and washed successively with methanol, THF, digas, and diethyl ether (10 ml / time). IR (compact beads): 2565 cm-(SH segment). Step 骒 E-Michael addition reaction: The resin (50 mg) from Step D was swelled in anhydrous N, N-dimethylformamide (1 ml), followed by cyclohept-2-en-1-one ( 70 microliters, 63 micromoles), and the mixture was shaken at room temperature. After 2 hours, the resin was decanted and washed successively with methanol, tetrahydrocondensing, digas, methyl ether, and diethyl ether (10 ml each). Step F-Reductive amination with amino acid: Resin (50 mg) from Step 泡 is swelled in dichloromethane (1 ml), and glycine third, butyl ester salt is added at room temperature under argon atmosphere. Acid salt (75 mg, 447 μmol), sodium sulfate (100 g, sodium triethyloxyborohydride (63 mg, 297 μmol), and acetic acid (10 μl), and the mixture was shaken for 24 hours Resin was filtered off and washed successively with water, methanol, tetrahydrofuran and digasmethane. Step G-Dissociate 1. Resin from the resin and deblock the amino esters: Resin from step F (50 (Mg) with trifluoroacetic acid (丨 ml) and triisopropylsilicon (20 µl) in dichloromethane (2 ml) at room temperature. After 3 hours, the resin was removed by filtration, and then the Gas methane washing (j 0 ml). After adding toluene (10¾ liters), the solution was concentrated and co-evaporated with toluene twice. The residue was dissolved in water (1 ml) and added to two Sep-Pak-boxes. (Waters Sep-Pak Plus). C &quot; silica was washed with water (4 ml), the final product was dissolved in 20% methanol and concentrated. From 5 ml After drying at Zhongliangkang, for example,-[3_ (1 · thiodecaline "galactosyl) cycloheptan-1-yl] glycine is obtained as a white powder (48 mg ^ * 1h_nmr_-110-ϋ) Standards are applicable to Chinese National Standards (CNS) Α4 specifications ~~ --- ~~ __ (谙 Please read the weeping on the back of the board before filling in this page)

1T i 4 6 7 9 Α7 B7 V. Description of the invention (108) It was decided that the ratio of known diastereomers was 10: 10: 8: 6. 111 · NMR (3 6 0 MHz, CD3OD, iso Structured protons): δ 4 · 36 (&lt; 1, Ji.2 = 9.6 Hz), 4.40 (d, Ji.z ^ 9 · 5 Hz), 4.44 (d,

Ji.2 = 9,1 Hz), 4.45 (d, J12 = 9.2 Hz); m / 2 estimates 値 Ci5H27N07S (M + H), 3 66.2, measured 値 366.1. Example 4 Inhibition of the combination of heat-unstable enterotoxin and GDlb In this example, this 1-thiogalactose derivative of formula I performs its inhibition of heat-unstable enterotoxin from coliform bacteria and gangliolipid GDlb The ability to combine. This bioassay was performed using the method described in A.-M. Svennerbliolni13, except that the ganglion lipid GDlb was used instead of the ganglion lipid GM1. Test examples A 1, A2., A4-A7, A10, All, Bl, B2, B4-B7, B10, B1 1, C2, C5, C7, CIO, C1 1, D2, D4, D5,

El, E2, E4, E10, Ell, FI, F2, F5, F7, F10, Printed bags for employees' cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs {Please read the note on the back before filling out this page}. ^ Τ ·

Compounds of Fll, G2, G5, 12, 15, and J7. All compounds have been tested to inhibit the combination of heat-labile enterotoxin and ganglioside GDlb by at least 20%, except for the compounds A2, A5, A7, CIO, D2 and G2, which cannot be inhibited at the concentration used in the analysis At least 20% binding "Example 5 Inhibition of the binding of cholera toxin and GDlb In this example, the 1-thiogalactose derivative of the above formula I was tested for its ability to inhibit the binding of cholera toxin to ganglioside Gmb. This bioanalytical method uses the step modification method described in A.-M. Svennerbholm13 to advance -111-This paper size is applicable to the Chinese National Standard (CNS) A4 specification (2iOX 297 feet) 46791 A7 B7 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Cooperative prints 5. Description of invention (109). On day 1, a microtiter plate (C96 Maxisorp) was coated with 100 microliters of 1 mg / ml GDlb (disialoganglioside Gmb, MW = 2127, Fluka) in PBS (per well), And incubated overnight at 37eC. On the second day, the sample to be tested was diluted in BSA-Tween-PBS (0.1% B S A and 0.0 5% Twee η 2 0 in P B S; S i g m a). A total of 500 microliters of each solution was prepared, so that each point could be detected four times. Roll curves of CTB5-HRP at 10, 20 'and 30 ng / ml were prepared (CT-B5 conjugated to HRP, Sigma, freeze-dried, and diluted in Tween-PBS). In the inhibition experiments, 20 ng / ml of CTB5-HRP was used. The samples were incubated for another 2 hours at room temperature. After incubation, the dishes were cleared, and the dishes were washed twice with 200 microliters of PBS per well to remove unadhered gangliosides. The plate was then incubated with 200 μl of 1% BSA in PBS (per well) at 37 ° C for 30 minutes to block additional binding sites on the plastic surface. The plate was re-emptied, and the plate was washed 3 times with 200 μl of 0.05% Tween 20-PBS (per hole) to remove the non-adherent BSA ^ sample (100 μl), added to 4 different holes, and placed in the chamber. Incubate at temperature for 30 minutes. The plates were cleared and washed with 200 microliters of 0.05% Tween 20_ PBS 3 times per well to remove unattached BSA. The substrate solution was freshly prepared in each ELISA. Each solution contained 10 mg of ortho-phenylenediamine (Sigma), 5 ml of 0.1 M sodium citrate (sterile filtration or autoclaving), 5 ml of 0.1 M citric acid (sterile filtration or autoclaving) and 4 ml of 30% Η202. (Gloves should be worn because the ortho-phenylenediamine association-112- This paper size applies to Chinese National Standard (CNS) A4 specifications (210X297 mm 1 ~ I 丨 -II (谙 Please read the precautions on the back before filling in this page)

, TT Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 481917 a? Β7 V. Instructions (110) Carcinogenic). The substrate solution (100 µl) was added to each well and incubated for 30 minutes at room temperature. After incubation, OD45q was recorded. Under the analytical conditions, D-galactose has an IC5 of 30 mM. value. Test examples A hA10, Bl_B6, B6A- B6L, B6Q, B6T, B7-B8, BIO, C1-C3, C5, C7, C8, CIO, D1-D5, D8, E1-E9, F1- F10, 〇2, G3 'G5-G10, H-2, H-3, H-5-H10, 11-13, I5_110' J1-J3 and J5-J10 compounds. All compounds tested inhibited the binding of cholera toxin and ganglion lipid Gdu by at least 20%, except for the examples Al, A3, A4, A6-A8, A10, Bl, B3, B4, B10, Cl, C3, C8 , D3, E5, E8, E9, F1, F5-F7, F9, F10, G3, G7-G10, H2, H5, H8.H10, 12, 18-110, J5-J10 compounds, the concentration used in the analysis Down will not inhibit binding for at least 205. (Ie 1 mg / ml). Example 6 'CT and LT Cytotoxic Neutralization In this example, the solid phase carrier of Example 2 was tested for its ability to neutralize cT and LT cytotoxicity. The cytotoxicity of C T and L T was detected using Chinese hamster egg cells (CHO), which were maintained in Hams F12 medium supplemented with 10% embryonic bovine serum (Fbs) at 37 ° C. (: 5% CO2 in the atmosphere. The toxin sample is diluted 1: 5 in Hams medium, and then sterilized through a 0.22 micron syringe filter. The sample is diluted 5 times in succession in the medium, and 100 microliters of each dilution is added to the hole. There is a confluent monolayer of CHO cells, which is incubated at 37 ° C for 24 '], hr (at 5% (: 02). Each sample is analyzed twice. __ -113- (CNS) Question A4 (21〇χ · ^^ Splash) (Please read the precautions on the back before filling in this page) Order ^ * τ · 4) 7917 Printed by A7 B7, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 2. Description of the invention (111) Cytotoxicity can be easily seen after 24 hours incubation. Compared with the control group containing no toxin, after 24 hours, the cells were fixed with 95% methanol and then stained with Geimsa dye. Toxin-containing samples from neutralization experiments were treated in a similar manner, except that the determination of the percentage of neutralization was compared to the endpoint dilution concentration of the sample with or without the solid phase carrier material of Example 2. Will contain pure CT or LT (2, 10 or 20 µg in 1 ml PBS) solution was added to the solid phase of Example 2 The body (20 mg) was placed in a 1.5 ml microcentrifuge tube and incubated at room temperature for 1 hour on an upside down spinner. After incubation, the solid carrier material was allowed to settle to the bottom of the tube, and the supernatant was carefully removed. Supernatant was added to CΗ0 cells, and the end point of cytotoxicity was determined after 24 hours incubation as described above. Compared with the control group of unreinforced phase carrier material, the degree of end point reduction was determined in the presence of solid phase carrier material. The results show that the solid phase carrier material of Example 2 can neutralize more than 90% of the CT and LT activities' regardless of the concentration of the toxin, that is, the remaining toxin activity is less than 10%. Example 7 Inhibiting colony-acting factor antigen (CFA cilia) Binding to blood type glycoproteins In this example, the 1-thiogalactose derivative of the above formula I was tested for its ability to inhibit the binding of CFA cilia to blood type glycoproteins. Bacterial surface adhesion antigens, such as CF A ciliate, have a The virulence factors can be expressed by certain enteric pathogens, including the enterotoxigenic strains of Escherichia coli. These cilia are important factors for the adhesion of bacteria to cell surface receptors. Therefore, CFA cilia bind to The purpose of the preparation is to determine whether the compound can inhibit pathogenic microorganisms. -114- The paper size applies the Chinese National Standard (CNS) A4 specification {21〇 &gt;: 297 mm.) (Please read the note on the back before filling in this page. }

Printed by the Consumer Standards of the Central Standards Bureau of the Ministry of Economic Affairs t 4 6 7/917 A7 ___B7 V. Description of the invention (112) Useful test for binding to cell surface receptors. The binding analysis was performed by coating 50 microliters of blood glycoprotein (10 micrograms / mL) in PBS in microtiter wells, 37. (: The solution was removed by aspiration for 2 hours, and the solution was replaced with 100 microliters of 1% BSA containing 0.05% Tween 20 in PBS (PBST), and incubated at 37 ° C for another 1 hour. Wash 200 μl PBST three times, and replace with biotinylated CF A 1 (5 μg / ml) in 50 μl PBS containing 0.05% BSA. After incubation at 37 * C for 2 hours After that, the binding reaction was stopped due to the aspiration of the solution, and the dishes were washed with PBST (3 x 200 μl). Avidin-peroxidase (50 μl of a 1/3000 dilution of 1 mg / ml solution was added to In PBST containing 0.05% BSA), incubate the plate for an additional hour. After washing the wells as described above, add 100 μl of the substrate solution (0.42 mM tetrabenzidine (TMB) in 0.1M sodium citrate buffer solution, pH 6.0, (Containing 0.5 μM urea peroxide), and the plate was incubated at ambient temperature for 10 minutes, the enzyme reaction was stopped due to the addition of 50 μl of 2N H2S04. Three binding assays were performed, and background binding was detected on the holes coated with BSA only値 "Binding inhibition assay was performed using oligosaccharides at a concentration of 1 mg / ml in PBS Inhibitors and biotinylated CFAI cilia (5 micro / ml) were first cultivated at 37. (: next 1 hour, and then added to microtiter holes coated with blood-type glycoproteins as described above. Utilize ortho -Cynyl phenyl-β-D-galactose is the control inhibitor in these experiments. Test Examples VIII-VIII 10, 81-: 68, 81.0, 〇1-〇3, 〇5 · C7, C8, CIO, D1-D5, D8, D10, E1-E10, F1-

I ____- 115 -_________ This paper size is applicable to China National Standard (CNS) A4 specification (210X297mm> (Read the f note on the back before filling this page)

4 6 7 9 1 A7 B7 V. Description of the invention (113) F10, G1-G3, G5-G10, H1-H3, Η5-Η 1 0, 11-13, 15-110, J1-J3 and J5-J10 1-thiogalactose derivatives. Among these compounds, the results show that the compounds of Examples B2, B5, Η2, Η3, Η5, Η6, Η7, Η8, Η9, Η1 0, II, 12 and 19 can inhibit the binding of CF AI cilia and blood group glycoproteins, Amount from 1 3 -7 1%. Compounds with histidine or tryptophan (H and I hydrazone) were particularly good inhibitors in this experiment. From the above description, various modifications and changes in the composition and method should be clear to the skilled artist. All such changes are included in the appended patent application parks to be included here. Printed by the Consumers' Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs -116- This paper is of a suitable size. It uses the Chinese National Standard (CNS) A4 specification (21 0 X 297 mm)

Claims (1)

Zhenggu No. 568 Patent Application Chinese Patent Application Amendment (December 89) Α8 Β3 CS D8 L a compound of formula I ... WITT ^ F · I S | R4 is the policy of the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, where R1 is selected from the following including hydrogen, (6-6 alkyl and phenyl); H2 is selected from hydrogen or Ci.6 alkyl; R3 is selected from hydrogen or Cm alkyl; Or R1 and R2, or R1 and R3 may be connected, and R1 and / or R2 protons may be added to form a cycloalkyl ring; R4 is -XR5, wherein X and R5 form an amine group, an amino group or an amino acid, selected from the following: Includes glycine 'β-alanine, leucine' histidine, tryptophan, and arginine; or X-NΗ- and R5 Η; Cu alkyl or (cycloalkyl; or R4 XC 0 R6 in which X is -N Η-and R6 is C. .5 alkyl or /-several groups; Υ is sulfur; Ra, Rb, Re and Rd are each independent and limited to Η and C2.I2 alkylcarbonyl * and η is 0 or 1; and a pharmaceutically acceptable salt thereof. 2. The compound according to item i of the patent application park, wherein the compound of formula I is an α-isomer. _ 3_ Compound according to item 1 of the scope of patent application , Where the compound of formula I is a β-isomer. Or R2 and R3, or rule 1, r2 &amp; r3 or R1 and / or R3 adhere to the recovered paper. The dimensions of the paper are applicable to the Chinese National Standard (CNS) A4 specification (21〇). χ297 mm) (Please read the minus item on the back first (Fill in this page) 'Pack-a 4679, patent application scope ABCD Printed by the male labor consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs of the Male Workers' Cooperatives 'where η is ο, r [& r2 connected' plus The carbon attached to the heart forms a cyclofluorenyl ring having 5 to 7 carbon atoms and optionally substituted by 1 to 3 alkyl groups. 5. The compound according to item 4 of the scope of patent application, wherein ... Connected, plus the carbon attached to it, to form a cyclopentane or cyclohexane ring. • The compound according to item 1 of the scope of patent application, where, when R1 and R are connected, plus R1, R2 and R3 are attached Carbon atom to form a cycloalkyl ring having 5 to 7 carbon atoms and optionally substituted with 1 to 3 alkyl groups. 7. The compound according to item 6 of the patent application park, wherein R 丨 and chi 2 The carbon atoms attached to R1, R2 and R3 are added together to form a cyclopentane, dimethylcyclopentane, cyclohexane, dimethylcyclohexane or cycloheptane ring. Compound of 6 wherein R4 is _XR5, where X is -NH- and R5 is cycloalkyl. 9. According to the scope of claim 1 When η is 1, R2 and R3 are connected, and the carbon atom attached thereto forms an n-pinene ring. 10, The compound according to item 1 of the patent application scope, wherein r4 is _xr5, where X and R5 The amino group forming amino group is selected from the following including glycine 'β'alanine, leucine' histamine, tryptophan, and arginine. U 'Compound according to item i of the scope of patent application Wherein, Min 4 is · χ &lt;: (〇) κ6, where X is -NΗ-, and R6 is methyl or 2-carboxyphenyl. The compound according to item 1 of the applied patent garden is selected from the group consisting of: 2-hydroxycyclopentan-1 _yl 1 _sulfur β-D-galactopyranosyl: y: 2 hydroxyl Cyclohex-1-yl 1-thio-β-D-galactopyranosyl paper standard (Chinese National Standard (CNS) A4 specification (21〇 &gt; &lt; 297mm)) (Please read the back Note: Please write this page again J 'Pack. Order 4 6 7 8 Staff Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China A8 Β8 C8 D8 6. Scope of patent application &quot;' 3-sherky-1-phenylbutane-1 -Yl 1-sulfur-0-1]) _? Galactolactone releases (3-¾-n-n-white-2-yl) methyl 1 · sulfur-β-D- p than galactolactone benefit 3- Hexyl-1-heptan-1-ylsulfanyl-β-D-T ^ b-galactopyranosyl: y: 3 ** Cyclopentyl 1-yl1-sulfanyl- (X_D p than galactopyranosyl-2, 2-Dimethyl-4 -hydroxycyclopentan-1 -yl 1-thio_ β-ο -galactopyranosyl 4-hydroxypentan-2-yl 1 -thio-β · D · galactopyranoside L2 -Difluorenyl-5-Cyclohex-1-yl1-thio | 1) -galactopyranosyl 3-Lycylcyclohex-1-yl-1 -thio-β-D-galactopyranofuran : y: 4,4 · dimethyl-3-hydroxycyclohex-1 · yl 1-sulfur j_D_ Galanose lane 2 -Aminocyclopent-1-yl 1-thio-β-Dp than galactopyranosyl-2 · aminocyclohexyl · 1-based 1 -thio-β-D-p galacto-3 -Amino-1-phenylbut-1-yl 1-sulfo-β-Dp galactophan turns to (3-amino-n-? White-2-yl) methyl galactophan 3_amine Cycloheptan, 1-yl 1-thio-β-D-galactopyranosyl: y: 2,2_dimethyl-4 -aminocyclopent-2-yl 1-thio-β_] 3-fluorene ratio Galacto ^: 3-aminocyclopent-1-yl1-thio-β-D-galactopyranofuran: y: 4-aminopentyl-2-yl 1-thio-β-D-pyran Galactose: y: 3-aminocyclohex-1-yl 1-sulfur β-D-galactopyranosyl 3-amino-4,4-dimethylcyclohex-1-yl 1-thio-0_ [) -1 »Bilan galacto selects: ^: 2 · Ethylamine amino group per -1 -yl 1 -sulfur -β-D-ρbiran galactoline_Oath 2 -Ethylamino amino group curtain _ 1_Base1_Sulfur-β-D_ρ Biran galactofen 3-Ethylamine · 1 · Bin-Butyl-1-yl-ρ Biran galacid Jingzhe 3 -Ethylamine Hept-1-yl 1-thio-β-Dp biran galacto dream 3-acetamidocyclopentan-1 -yl 1 -thio-β-Ε)-ρ galacto-3-this paper Standards: Chinese National Standard (CNS) A4 (210X2) 97 mm) (Please read the notes on the back before filling out this page) k. Order 467 Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 8 Β8 CS D8 VI. Application scope 4-Ethylamine-2 -Yl 1 -thio-β-D -galactopyranoside 3 -acetamidocyclohexyl 1 -thio-β -D -galactopyranoside 3 -ethylamino-4,4 -di-Tyl Cyclohexyl 1-sulfur-β-D-? Biran galacto-Co_Fen 2- (2-Chloroquinolamine) cyclopent-1-yl 1-Sero-β-Dp (! \ / 2- (2-Ethylamidoamino) cyclohex-1-yl1-thio-β-D-anan galactofen 3-(2-carboxybenzylamido) -1 -benzene Butyl-1 -yl 1 -thio-β-D-p-galactopyranoside [3- (carboxybenzylamido) n-fu-2-yl] methyl 1-galactopyranosyl 3- (2 · Epi-amino acid amine) cycloheptan-1-yl 1-thio-β-Dp than galactophan to 3- (2-chityl benzylamine) pent-2-yl 1-thio-β-Dp Bilanogalactoidea 5- (2 · Carboxamidinyl) -2,2-dimethylcyclohexyl-galactopyranoside for 3- (2-Chictyloctylamino) cyclohexyl-1 -Yl 1-thio-β-Dp galactopose / Nα- [2- (1-thio-β-D-galactopyranosyl) ring Pentyl-ryl] glycine &gt; ^-[2- (1-thizone-0-galactopyranosyl) cyclohex-1-yl] glycine N α-[4-phenyl-4- (1-thio-β-D-p than galactopyranosyl) butan-2-yl] glycine, Nct- [3- (U-sulfur-β-D-galactopyranosyl) methyl) n葙 · 2-yl] glycine Nα-DU-thiogalactopyranosyl) cycloheptyl_ 丨 _yl] glycine Nα- [3- (buthio-cx-D-galactopyranosyl) ring Heptyl-butyl] glycine [4,4-dimethyl-3- (1-thio-β ·: 〇_galactopyranosyl) cyclopentan-1-yl] glycine '---- ---- (; k I- (Please read the notes on the reverse side before filling out this page} -Order · 10, This paper size adopts China National Standard (CNS) Α4 Specification (21〇 &gt; &lt; 297 Public epidemic, ~~ — 8 8 88 ABCD Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 6. Application for patents Nct- [3- (l-sulfur-β-D -11 galactopyranosyl) cyclopentyl-1 -Yl] Glycine N &quot; ct- [4- (l-Sero-β-E) -p-galactopyranosyl) pent-2-yl] glycine N cc-[4,4-dimethyl- 3-(1 -thio-β -D -galactopyranosyl) cyclohexyl-1 -yl] glycine N α-[3-(1-thio-β -D -pyran Lactosyl) cyclohexyl-1-yl] glycine N α-[5-(1 -thio-β -D -galactopyranosyl) -2,2-dimethylcyclohex-1-yl] glycine Amino acid N β-[2-(1-thio-β-D-galactopyranosyl) cyclopentan-1 -yl] -β-alanine N β-[2-(1 -thio-β-D- Galactopyranosyl) cyclohexyl-1 -yl] -β-alanine Nβ- [4-phenyl-4- (1-thio-β-D-galactopyranosyl) but-2-yl]- β-alanine- Νβ- [3-((1 -thio-β-D-galactopyranosyl) methyl) n-fluoren-2-yl] -β-propylamine N β-[3-(1- Sulfur-β-D-galactopyranosyl) cycloheptan-1-yl] -β-alanine) N β-[4,4-dimethyl-3-(1 -thio-β-D -pyran Galactosyl) cyclopentan-1-yl] -β-alanine N β- [3-(1-thio-β-D-galactopyranosyl) cyclopentan-1-yl] -β-alanine N β-. [4-(1 -thio-β-D -galactopyranosyl) pentan-2-yl] -β-alanine Nβ- [4,4-dimethyl-3- (1-thio- β-D-galactopyranosyl) cyclohex-1-yl] -β-alanine N β-[3-(1 -thio-β -D -galactopyranosyl) cyclohex-1-yl] -β-alanine Nβ- [5- (1-sulfur-β-D · pyran galactose Group) -2,2-dimethylcyclohexyl-1 -yl] -β-alanine N ct-[2-(1 -thio-β -D -galactopyranosyl) cyclopent-1 -yl] -L -Leucine-5- This paper is sized according to the Chinese National Standard (CNS) A4 ^ # · (210X25 »7mm) (Please read the precautions on the back before filling this page) Ά ----- ------- Wide, install ------ ir ---- Α8 Β8 CS D8 467917 VI. Patent application scope Na- [2- (lkPDp than galactopyranosyl) cyclohex-1-yl ] 丄 _leucine Na- [4 -fluorenyl- 4- (1-thio-galactopyranosyl) butyl_2 &gt; • yl] L-leucine Na- [1- (1-thio-β- D-p galactopyranosyl) cyclo ^ heptan-3-yl] _L-leucine N a-[4,4-dimethyl-3-(1-thio-β-D-galactopyranosyl) ) Cyclopentyl 1-yl; JL-leucine Nα- [3- (1-Bro-β-D-p-galactopyranosyl) cyclopentyl] leucine Na- [4- (l-sulfur- β-Di »galactopyranosyl) pentan-2-yl] -L 'leucine N a-[4,4-dimethyl-3-(1-thio-β-D -galactopyranosyl) ) Cyclohexyl-1-yl] -L-leucine Nct- [3- (l-sulfur-β-D-p-galactopyranosyl) cyclohexyl-fluorenyl] leucine N a-[2- (1-thio-β-D-p galactopyranosyl Cyclopentyl_ 1yl] _ethyl_histidine N a-[2-(1 -sulfur-β-D-piranogalactoside) cyclohexyl-1_yl] _ L _histidine Ncc- [4-phenyl-4- (1-thio-β-D-11 galactopyranosyl) but-2-yl] L-histidine N a-[3-(1-thio-β-D- p-galactopyranosyl) cycloheptan-1 -yl]-^ histidine Nα- [4,4-dimethyl-3-(1-thio-β-D-p-galactopyranosyl) ring Pentamyl 1-yl] -L-histamine Ssl N a-[3-(1-sulfuryl-β-D-galactopyranosyl) cyclopentyl- 丨 _yl] · Histamine Na- [4- ( l-sulfur-p-D-i1 galactopyranosyl) pentan-2-yl] _L-histidine N a-[4,4-dimethyl-3-(1-sulfur-β-D-ρ Galactopyranosyl) cyclohexyl-1-yl] -L-histidine Nα- [3- (1-thio-β-D-p galactopyranosyl) cyclohexyl] -histidine N a- [2-(1 -Sulfur-β-D-p-galactopyranosyl) cyclopentyl-〗 _ 基] _ L _Tryptophan-6- This paper is commonly used by China National Standards (CNS) (210X297 mm) (He Xianmin tt on the back of He Xianmin wrote this page} -Reorder.10. Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs $ 1 4 6 &quot; 7 9 1 A8 B8 C8 D8 Economy Yin Yangbiao The scope of patent application of the printed bag of the Bureau of ZhengGong Consumer Cooperative Co., Ltd. (1-^-(3_D-galactopyranosyl) butyl "_yl] _L-tryptophan 1 ^-[3- (1-thio-o-galactopyranosyl) cycloheptyl_1_ Yl] 丄 -tryptophan Nα- [4,4-dimethylgalactopyranosyl) cyclopentane · 1-yl] -L-tryptophan Nα- [3- (1-thio-β-D-pyridine Galactopyranosyl) cyclopentyl group] _L_tryptophan, [4- (1-sulfur + 〇 "galactopyranosyl) pentan-2-yl] _; 1_tryptophan 14 1- [454-dimethyl-3- (1-sulfur-13_1:) _ (7-galactopyranosyl) cyclohexyl_1-yl] -L-tryptophan Nα- [3- (l-sulfur -β-D-galactopyranosyl) cyclohexyl_1-yl; l · tryptophan acid Na- [2- (l-thio-β-D-galactopyranosyl) cyclopentylbuspermine Acid Na- [2- (l-thio-β-DP galactopyranosyl) cyclohexyl_1-yl] _L_arginine acid Na- [4-phenyl-4- (l-sulfur-β-; 〇_galactopyranosyl) but-2-yl] _L-arginine N ex-[3-(1 -thio-β-D-galactopyranosyl) cycloheptyl_ 丨 _yl] · L -fine Amino acid N a-[4,4-dimethyl-3-(1-thio-β-D-galactopyranosyl) cyclopentyl_ 1 -yl] -L-arginine N a-[3 · (1-thio-β D -galactopyranosyl) cyclopentyl 丨 丨 kib L _arginine Nα- [4- (1- Sulfur-β-Dp galactopyranosyl) pent-2-yl] _l_arginine N a-[4,4-dimethyl-3-(1-thio-β-D-galactopyranosyl) ) Cyclohexyl 1-yl] -L-arginine. Να- [3- (1-thio-β-Dp galactopyranosyl) cyclohexyl_yl] _l_spermine 2'2-— Fluorenyl-4- (methylamino) cyclopent-1-yl 1-thio-0_〇- (! Bran galacid paper size applies to China National Standard (CNS) A4 (2I0X29? Mm) ( (Please read the notes on the back before filling this page) —.k_ Order printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A8 B8 C8 P8 _ VI. Patent application scope Glycoside 2, 2 -dimethyl-4-(iso Alanyl) cyclopentyl-butylthio-p-galactopyranosyl 2.2-methyl-4- (n-propylamino) cyclofluoren-1-yl 1-thio-glucose 2.2-dimethyl _4 _ ((foot) _second butylamino) cyclopentyl_1_yl 1_thio-0-〇-galactopyranosyl aluminum 2.2-dimethyl-4-((3) -second butylamino ) Cyclopent-1-yl 1-thio-0-〇-galactopyranosyl aluminum 2.2-fluorenyl-4- (pent-3-yl (Cyclopentyl-1-yl 1-sulfur-P_D-p) galactosyl diamond. 2,2-Dimethyl-4_ (n-hexylamino) cyclopentyl-1 -yl 1-sulfur-β-D- Galactopyranosylpyrene 2,2 · dimethyl_4- (cyclobutylamino) cyclopent-1-yl 1-thio-β-D-galactopyranosyl 2.2-dimethyl_4- (3 , 3-Dimethylcyclobut-1-ylamino) cyclopentyl-butyl1-thio-β-D-galactopyranosylpyrene 2.2-dimethyl-4- (cyclopentylamino) cyclopentyl- 1-yl 1-thio-β-D-galactopyranoside 2.2-dimethyl- 4- (3-methylcyclopent-1-ylamino) cyclopent-1-yl 1-thio-β- D-p galactopyranosyl 2.2-dimethyl-4- (3,3-diamidinocyclopent-1-ylamino) cyclopentan-1-yl 1-thio-β-D-pyran Lactosides 2,2-dimethyl-4-(cyclohexylamino) cyclopentan-1 -yl 1 -sulfur -β -D -analban-8-This paper is based on China National Standards (CNS) A4 specification (210X297) I -I---I!-^-1 I n (Please read the precautions on the back before filling this page) ABCD IS 7 9 1 7 VI. Patent application scope Lactose 甞 2,2 -Difluorenyl_4_ (3-methylcyclohex-1-ylamino) cyclopentyl-1_yl 1_thio-β-D-galactopyranoside 2'2_dimethyl-4- ( 4 -Methylcyclohex-1-ylamino) cyclopent-1-yl 1-sulfo-β-D-galactopyranosylpyrene and its pharmaceutically acceptable salt e.13. A compound for inhibiting the binding of a toxin to its receptor 'or the binding of an organism to its cell surface receptor. 14. A compound according to item 13 of the scope of patent application, wherein the toxin is a heat-labile enterotoxin or cholera toxin. 15. The compound according to item 13 of the patent application, wherein the organism is an enterotoxin-producing strain of Escherichia coli or Escherichia coli. 16. The compound according to item 13 of the patent application, wherein Formula I Compound θ α -isomer. 17. The compound according to item 13 of the scope of patent application, wherein the compound of formula .1 is a β-isomer. 18. The compound according to item 13 of the scope of patent application, wherein when η is 0, rt and R2 are connected, and the carbon to which it is attached is formed to have 5 to 7 carbon atoms and optionally 1 to 3 alkanes Cycloalkyl. 19. The compound according to item 13 of the scope of the patent application, in which when n is ii and R2 are connected 'plus the carbon atoms to which r1, r2 and R3 are attached, forming 5 to 7 interfering atoms and optionally 1 to Cycloalkyl substituted by 3 gauge groups. 20. The compound according to item 19 of the application, wherein R4 is _XR5, wherein X is -NH- and R5 is cycloalkyl. -9-The standard of this paper is the Chinese national standard rate (CNS &gt; Α4 is now (210 × 297 mm)) tv-- (#Xian Min read the note on the back ^ ^ then fill out this page j-order the Ministry of Economic Affairs Central Standard Vehicle Bureau The industrial and consumer cooperatives printed 6 η Q for the scope of patent application A8 B8 C8 D8. For the compound in the scope of the patent, the order, r2, and the carbon atoms attached to it, to form a positive women's ring. According to the 13th continuation of the patent application, m ;, its tX and R5 form an amine group, a hydroxyl group or an amino acid 'is selected from the following including glycine, β-alanine, leucine, histamine 'Tryptophan and arginine; or R 疋 -XC (0) R6, wherein, and the ruler 6 is a sub or phenyl group. 23. A soothing animal that binds toxins and its receptors in the body or the organism A medicinal composition related to its receptor binding, which contains 99% of a pharmaceutically acceptable carrier, and at least 99% by weight of at least one compound of the formula]: '.. .. v'k— ( (Please read the following on the back: General matters before filling in this page) R4 is included in the booklet section of the bookkeeping department. N1 is selected from the group consisting of hydrogen, 6 alkyl and phenyl; R2 is selected from hydrogen or Cu alkyl; R3 is selected from hydrogen or CU6 alkyl; or R 1 and R · 2, or R 1 and R 3, or r 2 and ruler 3, or ruler 1, R 2 and R 3 can be connected, plus R1 and / or R2, or R1 and / or _R3 adhesion The broken atom forms a cycloalkyl ring; R4 is -XR5, in which X and R5 form an amine group, a base group or an amino acid, -10- this paper standard (CNS) A4- (210X297 mm) 6 4 Economy Ministry of Economic Affairs, Central Bureau of Work, Consumer Cooperatives, Counseling cs _____D8 6. The scope of the patent application is selected from the following including glycine 'β-alanine, leucine, histamine, tryptophan, and arginine; or X series -N Η-and R3 are Η; C 8 is radical or cycloalkyl: or R4 is &lt;: 0 to 6 which is -NΗ_ and alkyl or 2-carboxyphenyl; Y is sulfur; Ra, Rb, 1 ^, and 11 (1 are each independent and limited to fluorene and C2,12 alkylcarbonyl, and η is 0 or 1; and a pharmaceutically acceptable salt thereof. 24. A pharmaceutical composition according to item 23 of the scope of patent application Where ^ is 0, R1 and R2 are connected, plus The adhered carbon forms a cycloalkynyl ring having 5 to 7 carbon atoms and optionally substituted by 1 to 3 alkyl groups. 25. The pharmaceutical composition according to item 23 of the patent application park, where η is 1, R1 and R2 are connected, and the disk atoms to which R1, R2 and R3 are attached form a cycloalkyl group having 5 to 7 carbon atoms and optionally 1 to 3 alkyl groups. 26. The pharmaceutical composition according to item 25 of the patent application, wherein r 4 is .-XR5, where X is -NΗ- and R5 is cycloalkyl. 27. The pharmaceutical composition according to item 23 of the patent application, wherein When η is 1 'R2 and R3 are connected' plus the carbon atom to which it is attached, the orthorhomogeny ring e is formed. 28. According to the pharmaceutical composition of the 23rd item of the patent application, where r4 is' _XR5, where X and R5 forms an amine, hydroxyl or amino acid, selected from the group consisting of glycine β-. Alanine, leucine, histidine, tryptophan, and arginine; or R4 is -XC (0) R6 ' Where X is -ΝΗ- and R6 is methyl or '2-carboxyphenyl. -11-This paper size is applicable to Chinese national standard (CNS> Λ4 specification (210X297 mm) (Please read the first Please fill in this matter if necessary.) Order 6 4 b AS B8 C8 D8 Patent Application Scope Central Bureau of Standards, Ministry of Economic Affairs W: Industrial and consumer cooperatives print 29 'Pharmaceutical composition according to item 23 of the scope of patent application, where the compound is Is selected from the group consisting of: 2-hydroxycyclopentan-1 -ylthione-p-D-galactopyranosyl: y: 2-hydroxycyclohexyl-1 -yl1-thio-β-D-pyran Carbolactose Station 3-Ethyl-1-phenylbut-1-yl1-thio-β-D-p-galactopyranosyl (3-hydroxy-n-syn-2-yl) methyl1-sulfo-P- D-galactopyranosyl: y; 3-hydroxycyclocone-1 -ylsulfanyl-β-D-galactopyranosyl 3-hydroxycycloheptan-1 -yl 1 -thio-ct -D -pyran Lactose: y: 2,2-monomethyl-4-light-cyclopentyl-1-yl 1-thio-β-Dt »galactopyranos 4-hydroxypent-2-yl 1-thio-β D _ Galactopyranoside 2 j 2 --- methyl-5-glutamyl-1 -yl 1 -thio-β -D -if galactopyranosyl 3 -hydroxy ring i-1 -yl 1 -thio-β -D. Pyranose, 4,4-dimethyl-3-light-based cyclohex-1-yl 1-sulfur-β-Dp is less than 2-aminocyclopentan-1-yl 1-sulfur-β-D-galactopyranosyl 2-aminocyclohex-1-yl1-sulfur -β-D-aluminum galanose 3-amino-1-phenylbut-1-yl 1-thio-β-D-p than galactopyranoside. (3-Amino? White-2-yl) methyl 1-thio-β-Dp galactose · ^ 3-aminocycloheptan-1 -yl 1-thio-β-D-galactopyranosyl 2,2- · — Methyl-4-aminocyclofluoren-1-yl 1-thio-β-Dp galactose 3-aminocyclopentan-1-yl 1-thio-β-D-galactopyranosyl 4-amine Stilbene-2-yl 1-thio-β-D- * 7 galactophan 3-aminocyclohexyl-1-yl-1 -thio-β-D-galactopyranosyl: y: 3-amino -4,4-dimethylcyclohex-1-yl1-thio-0_ £) -1: Biran galactophan 2 -acetamidocyclopentyl-1 -yl 1 -sulfur-β-D- Asthma and breast milk alley Gangan (please read the precautions on the back before filling this page) -12- This paper size applies to Chinese National Standard (CNS) Α4 is present (210X297 mm) 4 6 7 9 Printed by J Industrial Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Α8 Β8 C8 D8 Aminocyclohexyl-1 -yl 1 -thio-β-D-p galactopyranosyl 3-Ethylamino-1-phenylbut-1-yl 1-thio-β-Dp galactopyranosyl 3 -Ethylaminocycloheptan-1 -yl 1 -thio-β -D -galactopyranosyl 3 -Ethylaminocyclopentan-1-yl 1-thio-galactopyranosyl: y: 4- Ethylaminopentyl-2-yl 1-thio-p-Dp galactopyranosyl: y: 3-Ethylaminocyclohexyl 1-sulfo-β-D-p galactopyranosyl: y: 3-ethyl Pro-Amino-4,4-dimethylcyclohexyl 1-thio-galactopyranosyl 2- (2-Ethylamino) cyclopent-1-yl1-thio-p_D_p galactopyranosyl 2-(2-Epibenzylamidinylamino) cyclohexyl-1 -yl 1 -thio-β-d -galactopyranosyl 3- (2-benzylbenzylamino) -1-phenylbutyl- 1-based 1_thio_ 卩 _]:) _ said galactophan. [3-(carboxyamido) n-pyridin-2-yl] methyl 1_thio-β_d-galactopyranosyl甞 3-(2-benzylbenzylamino) cycloheptan-1 -yl 1 _sulfur_β_d -Galactopyranosyl 3- (2-aminoalkylamino) pentan-2-yl-1 -thio-β-d-ρ galactophan 5- (2-carboxyamido) -2 , 2-Dimethylcyclohexyl-1_yl1_thio_0_1;) _ galactopyranosyl 3-(2-carboxybenzylamino) cyclohexyl-1_yl1_thio_β_D_ p Galanose Station Nα- [2- (1-thio-β-D-galactopyranosyl) cyclopentyl-pyl] glycine Nex-[2-(1-thio-β-D- p-galactopyranosyl) cyclohexyl- 丨 -yl] glycinate Nct- [4-phenyl- 4- (1-thio-β-Dp galactopyranosyl) butan-2-yl] glycinate Ν α-[3-((1 -thio_ β-D -galactopyranosyl) methyl) n-pyridinium_ 2 _yl] glycine-13- This paper applies Chinese National Standard (CNS) 8-4 Yi Pan {Please read the note on the back before filling in this page; | -.k ·-. Order t Printed by the Central Government Bureau of the Ministry of Economic Affairs and Consumer Cooperatives Βδ C8 D8 六 、 Application for patents N α-[ 3-(1 -thio-β -D -galactopyranosyl) cycloheptan-1-yl] glycine N α-[3-(1 -thio-a-D -galactopyranosyl) cycloheptan -1 -yl] glycine No ot-[4,4-dimethyl-3-(1 · sulfur-β-D- Galactopyranosyl) cyclopentan-1-yl] glycinate N ct-[3-(1 -thio-β-D-ρ galactopyranosyl) cyclopentan-1-yl] glycinate N α- [4-(1 -thio-β -D -galactopyranosyl) pentan-2-yl] glycine N α-[4_, 4 -dimethyl-3-(1 -thio-β-D- Galactopyranosyl) cyclohexyl-1 -yl] glycinate N cx-[3-(1-thio-β-D -galactopyranosyl) cyclohexyl-:!-Yl] glycinate N α -[5-(1-Sulfur-β-D-galactopyranosyl) -2,2-dimethylcyclohexyl-butyl] glycine-N β-[2-(1 -thio-β- D-galactopyranosyl) cyclopentan-1-yl] -β-alanine N β- [2-(1-thio-β-D-galactopyranosyl) cyclohex-1-yl: I- β-alanine N β-[4-phenyl-3-(1 -thio-β -D -galactopyranosyl) but-2- 2-yl] -β -alanine _ β-[3-(( 1-thio-β-D-galactopyranosyl) fluorenyl) n-fluoren-2-yl] -β-alanine N β- [3-(Buthio-β-D-galactopyranosyl) ring Hept-1 -yl] -β-alanine N β-[4,4-dimethyl-3-(1 -thio-β-D -galactopyranosyl) cyclopent-1 -yl] -β- Alanine N β-[3-( 1-sulfur-β-D-ρ-galactopyranosyl) cyclopent-1-yl] -0-alanine N β- [4-(1-sulfur-β-D -pyran galactosyl) pentan- 2 -yl] -β-alanine N β-[4,4-dimethyl-3-(1 -thio-β-D -galactopyranosyl) cyclohexyl-pyl] -β-alanine- 14- (Please read the notes on the back before filling in this page): k * 1T This paper size is applicable to Chinese National Standard (CNS) A4 scale (210X297 mm) 4679 Α8 Β8 C8 D8 VI. Patent Application Scope β- [3-(1 -thio-β-D-galactopyranosyl) cyclohex-1-yl] -β-alanine Nβ- [5- (1-thio-β-D-galactopyranosyl) -2,2 -dimethylcyclohexyl-1 -yl] -β-alanine N ex-[2-(1 -thio-β-D -galactopyranosyl) cyclopent-1 -yl] -L -Leucine N α-[2-(1 -thio-β-D -galactopyranosyl) cyclohexyl-1 -yl] -L -leucine N α-[4 -phenyl-4-( 1-thio-β-D-galactopyranosyl) but-2-yl] -L-leucine N α-[1-(1-thio-β-D-galactopyranosyl) cycloheptan- 3 -yl] -L-leucine N α-[4,4-dimethyl-3-(1 -thio-β-D -galactopyranosyl) cyclopentane- 1 -yl] -L-leucine N α-[3-(1-thio-β-D -galactopyranosyl) cyclopentan-1 -yl] -L -leucine Nct- [4- ( Buthio-β-D-galactopyranosyl) pent-2-yl] -L-leucine N α-[4,4-dimethyl-3-(1 -thio-β -D -pyran Galactosyl) Cyclohexyl-1-yl] -L-Leucine Printed by the Consumers' Cooperative of the Central Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling this page) Ν α-[3-(1 -Thio-β-D-galactopyranosyl) cyclohexyl-1-yl] -L-leucine Nα- [2- (1 -thio-β-D-galactopyranosyl) cyclopentyl-1 -Yl] -L-histidine N a- [2-(1 -sulfur-β-D-p-galactopyranosyl) cyclohexyl-1 -yl] · L -histidine N α-[4- Phenyl-4-(1 -thio-β -D -galactopyranosyl) butyl-2 -yl] -L -histidine No ot-[3-(1 -thio-β -D -pyranylpyranyl) Lactosyl) cycloheptan-1 -yl] -L -histidine N α-[4,4-dimethyl 3-(1 -thio-β -D-ρ galactopyranosyl) cyclopentyl-1- Group] -L-histidine N ex-[3-(1-thio-β-D -galactopyranosyl) cyclopentyl-2 · yl] -L -histidine N α-[4-(1 -Thio-β-D-galactopyranosyl) pentyl- 2 -Base] -L -Histidine-15- This paper uses Chinese National Standard (CNS) A4 size (210 × 297 mm) 4 9 7 6 ABCD 6. Scope of patent application (Please read the notes on the back first Fill out this page again) Ν α-[4,4-dimethyl-3-(1 -thio-β -D d-galactopyranosyl) cyclohexyl-1 -yl] -L -histamine N ct-[ 3-(1-thio-β-D-galactopyranosyl) cyclohexyl-1-yl] -L-histidine N α-[2-(1 -thio-β-D -galactopyranosyl) ) Cyclopentyl-1-kib L-tryptophan N ¢ x- [2- (l-sulfur-β-D-galactopyranosyl) cyclohexyl-l-yl] -L-tryptophan No ot -[4-phenyl-4-(1 -thio-β-D -galactopyranosyl) butan-2-yl] L -tryptophan No ot-[3-(1 -thio-β-D- Galactopyranosyl) cycloheptan-1 -yl] -L-tryptophan N α-[4,4-dimethyl-3-(1 -thio-β -D -galactopyranosyl) cyclopentyl -1 -yl] -L-tryptophan Nex-[3-(1-thio-β-D -galactopyranosyl) cyclopentan-1 -yl; L -tryptophan N α-[4- (1 -thio-β -D -galactopyranosyl) pent-2-yl] -L -tryptophan N cx-[4,4-dimethyl-3-(1 -thio-β -D- Galactopyranopyran Glycosyl) cyclohex-1-yl] -L · tryptophan acid Ministry of Economic Affairs Central Laboratories Bureau Consumer Cooperatives Cooperative policy N α-[3-(1-thio-β-D-galactopyranosyl) cyclohexyl -1 -yl] -L -tryptophan N a- [2-(1-thio-β-D -galactopyranosyl) cyclopent-1 -yl] -L -arginine N a- [2 -(1-thio-β-D-galactopyranosyl) cyclohexyl-1-yl] -L-spermine N α-[4-phenyl-4-(1-thio-β-D -pyridine Galactosyl) butyl-2-yl] -L-arginine No ot-[3-(1 -thio-β-D -galactopyranosyl) cycloheptan-1 -yl] -L -spermine Acid N cc-[4,4-dimethyl-3-(1 -thio-β -D -galactopyranosyl) cyclopent-1-yl] -L -arginine · Ν α-[3- (1-thio-β-D-galactopyranosyl) cyclopentane-1-yl] -L-arginine N cx-[4-(1-thio-β · D -galactopyranosyl) pentanyl -2 -Base] -L -Arginine-16- This paper size applies to 1 national standard (CNS) Α4 size (210 × 297 mm) of 1 country. Order of the Central Standards Bureau of the Ministry of Economic Affairs, Consumer Work Cooperative, Yindong A8 B8 C8 D8 Application Patent Fan Yuan 'Μα · μ, 4 · dimethyl_3_ (u ^ -P_d_galactopyranosyl) cyclohex-1 -yl] -L_spermine Of '2-Methyl-4- (methylamino) cyclopent-1-yl-thiogalactopyranoside 2,2-dimethyl-4- (isopropylamino) cyclopent-1-yl-1 _Thio_p_D-galactopyranoside 'methyl- 4- (n-propylamino) cyclopent-1-yl 1-thio-β-Dp galactopyranoside 2.2-dimethyl-4 _ ((R) _Second-butylamino) cyclopentyl- 丨 -galactopyranoside 2.2-dimethyl_4 _ ((s) _Second-butylamino) cyclopentyl, galactopyranoside 2.2-dimethyl, 4_ (pent_3-ylamino) cyclopentyl group-thio ^^, galactoaluminum 2,2-diamidyl ** 4- (n-hexylamino) cyclopent-1-yl 1-Sulfur β-D-galactopyranoside 2,2-methyl-4- (L-butylamino) cyclopent-1-yl1-thio-β-Dp Methyl-fluorenyl-fluorenyl-dimethylcyclobutyl- ^ ylamino 丨 cyclopentyl- 丨 -yl 1-thio-β-D-galactopyranosyl 2'2--fluorenyl 4- (cyclo Pentylamino) cyclopent-1-yl 1-thio-β-Dp galactose 2.2-difluorenyl-4- (3-fluorenylcyclopent-1-ylamino) cyclopentan-1-yl 1 _; ^ -β-D -galactopyranoside-17- The size of the paper is applicable to the Chinese National Standard (CNS) Α4 threat (210 ×: 297 mm) ---- ---- v'k-- (Please read the notes on the back before filling out this page)-, '1T 46791 7 Α8 BS C8 D8 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 6. The scope of patent application' Bis-dimethyl ^-^ dioxoylcyclopentyl-phenylamino "p-pentyl- ^ yl 1-sulfur-β-D-galactopyranosyl station 2,2 monomethyl-4- (cyclohexyl Amino group) cyclopent-1-yl 1-thio-β-D-i1 galactopyranoside 2,2_dimethyl-4- (3-fluorenylcyclohex-1-ylamino) cyclopentyl-丨 _ ^^-D-D-galactopyranosyl 2,2-dimethyl_4_ (4-methylcyclohexyl-butylamino) cyclopentyl 丨 _thio_β-D .pyran Galactose and its pharmaceutically acceptable salts. 30. The pharmaceutical composition according to item 23 of the application, wherein the toxin is a heat-labile enterotoxin or cholera toxin. 31. The pharmaceutical composition according to item 23 of the application, wherein the organism is cholera or enterotoxin-producing strain of Escherichia coli. 32. The pharmaceutical composition according to item 23 of the application, wherein the compound of formula I is an OC-isomer. 33. The pharmaceutical composition according to item 23 of the application, wherein the compound of formula I is a β-isomer. 34 'The pharmaceutical composition according to item 23 of the scope of the patent application, wherein when ^ is 0, R1 and R2 are connected, and the carbon attached thereto is formed to have 5 to 7 carbon atoms and 1 to 3 as required Cycloalkyl substituted with an alkyl group. 35. The pharmaceutical composition according to item 23 of the patent application park, where ^ is 1, R1 and R2 are connected 'plus the carbon atoms to which R1, R2 and R3 are attached to form 5 to 7 carbon atoms and the Desirable is cyclopo substituted with 1 to 3 alkyl groups. -18 · The size of this paper is applicable to the Chinese National Standard (CNS) Α4 (210X297 mm) (Read the notes on the back of the poem before filling in this page) '¥ Order βΊ 91 Α8 Β8 CS D8 Consumer Cooperatives Co., Ltd. 6. Application scope of patent 36. The pharmaceutical composition according to item 35 of the scope of application for patent, where R4 is _xr5, where X is _NH-aR5 is cycloalkyl. 37. The pharmaceutical composition according to the scope of the patent application_23, wherein when n is 1 'R2 and R. Connected together with the carbon atoms attached to it to form a positive blessing ring. 38. The pharmaceutical composition according to item 23 of the scope of patent application, wherein R4 is _XR · 'wherein X and R5 form an amine group' or amino acid is selected from the group consisting of glycine, β-alanine, Leucine, histidine, tryptophan, and arginine; or R4 is -XC (0) R6, where X is -N-, and R6 is methyl or 2-carboxyphenyl. 39. A carrier containing a 1-thiogalactose derivative, including _ including a carrier on which a plurality of at least one compound of formula I 'is covalently linked, Rc〇.0Rd R3 · 丨 _ 〇R = &gt; ~ R1 R2 wherein R1 is selected from the following including hydrogen, C! -6 alkyl and phenyl; R2 is selected from hydrogen or Ci.6 alkyl; R3 is selected from hydrogen or Cb6 alkyl; or R1 and R2, or R1 and R3, or R2 and R3 ′ or R1, R2 and R3 may be connected, and the carbon atoms attached to R1 and / or R2, or R1 and / or R3 may form a cycloalkyl group, R4 is -XR5, wherein X and R5 Amine group, hydroxyl group or amino acid, -19- This paper size is applicable to Chinese National Standard (CNS) A4 (210x297 gram) (Note on the back of Min Jing, please fill out the ear j. Order 4 6 7 9 1 7 A8 B8 C8 D8 The Consumer Cooperative of the Ministry of Economic Affairs of the Central Government Bureau of the People's Republic of China. 6. The scope of patent application. It is selected from the following including glycine, 3-alanine, leucine, histamine, tryptophan, and Arginine; or X-NH- and R5 Η; C ^ 8 alkyl or cycloalkyl; or R, XC0r6 where X is -NH- and R6 is Ci-W or 2-carboxyphenyl Y-type sulfur; RR, RC and Rd are independent of each other Limited to η and C2. 2 alkylcarbonyl groups, and η is 0 or 1; and a pharmaceutically acceptable salt thereof, the restriction is that only one of R1, R2, chi3, r5, r6, Ra, Rb, rc and Rd Link to the carrier. 40. The carrier containing a thiogalactose derivative according to item 39 of the scope of the patent application, wherein the carrier is a solid phase carrier. 41. The content according to item 39 of the patent scope 1'-thiogalactose derivative carrier 'wherein the compound of the formula Γ is an α-isomer. 42. According to the scope of the patent application No. 39, the "thiogalactose derivative-containing carrier' wherein the compound of the formula Γ is β-isomer. 43. According to the scope of the patent application No. 39, containing a thiogalactose derivative, wherein π is 0, R1 and R2 are connected, and the carbon to which they are attached forms a compound having 5 to 7 carbon atoms and optionally substituted cycloalkyl groups with 1 to 3 alkyl groups. 44 'A carrier containing a thiogalactose derivative according to item 39 of the patent application' wherein η is 1, R1 Connected to R2, plus the carbon atoms attached to Ri, r2iR3 to form 5 to 7 carbon atoms and optionally to 3 to 3 carbons Substituted cycloalkyl. 45. According to the scope of the application for patent No. 44 containing sulfur galactose derivatives-20-This paper is suitable for Guanjia County (CNS) (21GX297 mm) (Please read the back Note for refilling this page) Binding · 467 S Α8 Β8 C8 D8 Printed 'Scope of Patent Application' printed by the Consumer Goods Cooperative of the Central Office of the Ministry of Economic Affairs, where R4 is -Xr5, where χ is _nh_iR5 is cycloalkyl. 46. According to item 39 of the scope of application for a patent containing a 1-thiogalactose derivative, wherein n 疋 1, R2, and R3 are connected, and the lack of carbon atoms to which they are attached forms a n-pinene ring. 47. A carrier containing a 1-thiogalactose derivative according to item 39 of the scope of the patent application: wherein the compound can inhibit the binding of a toxin to its receptor, or the compound can inhibit the binding of an organism to its cell surface receptor. 48. A carrier containing a prothiogalactose derivative according to item 47 of the scope of the patent application, wherein the toxin is a heat-labile enterotoxin or Vibrio cholerae. According to Item 47 of the scope of patent application, the organism in which the thiogalactose derivative-containing carrier is contained is an enterotoxin-producing strain of orphan cholera or Escherichia coli. 50. The carrier containing a thiogalactose derivative according to item 47 of the scope of the patent application, wherein the carrier is a solid phase carrier. 5L 2 A carrier containing a thiogalactose derivative according to item 47 of the patent application 'wherein the compound of the formula Γ is an α-isomer. According to Item 47 of the scope of the patent application, a carrier containing a _thiogalactose derivative 'wherein the compound of the formula Γ is a β isomer. 53 _The content containing thiogalactose derivatives according to item 47 of the scope of the patent application. Where η 疋 0, R 1 and R2 are connected, and the adhesion is broken to form 5 to 7 carbon atoms. And if desired, a cycloalkyl ring substituted with 1 to 3 alkyl groups. 54 · According to the scope of the patent application No. 4 7 contains 1 _ thiogalactose (please read the precautions on the back before copying this tile) Order 467 9; 7 A8 B8 C8 D8 Patent application body 'where n is 1, connected, plus the carbon atoms attached to R1, ruler 2 and ruler 3 to form 5 to 7 carbon atoms and 1 to 1 as needed Cycloalkyl substituted with 3 alkyl groups. 55. The carrier containing a 1-thiogalactose derivative according to item 54 of the scope of the patent application, wherein R4 is -XR5, wherein X is -NH- and R5 is a cycloalkyl group. 56, according to item 47 of the scope of the patent application, a carrier containing a thiogalactose derivative 'is used, wherein when η is 1, R2 and r 3 are connected' plus a carbon atom to which they are attached to form a regular woman ring. 57, a pharmaceutical composition that relieves the body's disease-associated disease toxins and its receptors or to organisms and cell surface receptors, which contains 1-99% by weight of a pharmaceutically acceptable carrier, and 1 -9-9wt% of a carrier containing a 1-thiogalactose derivative, which includes a carrier having a plurality of compounds of the formula Γ covalently linked thereto: ^ _ ^ 1 _ _ ·-Tit m · ml m In 1 ^ 11 OJ (Please read the notes on the back before filling out this page) R4 is printed by the Consumer Cooperative of the Central Operating Bureau of the Ministry of Economic Affairs where R1 is selected from the following including hydrogen, Cu alkyl and phenyl; R2 is selected from hydrogen or Cy alkyl; R3 is selected from hydrogen or Cu alkyl; or R1 and R2, Or R1 and R3, or R2 and R · 3 'or R1, R2 and R3 -22- The standard of this paper is applicable to the Chinese national standard (0?) 8 4 grid (210 father 297 male) 679 4 and / or R2, Or the carbon source A8 B8 C8 DS attached to ruler 1 and / or R3 can be linked, and the R 1 proton is added to form a cycloalkyl ring; R4 is -XR5, where X and r5 form an amine group, a compliant group, or Amino acids selected from the group consisting of glycine, β-alanine, leucine, histidine, tryptophan, and arginine; or X-NΗ- and R5 Η; Cu alkyl or naphthenic Or R4 is XCOR6 where X is -NH- and R6 is C. 5 alkyl or 2-carboxyphenyl; Y is sulfur; Ra, Rb, Re and Rd are each independent and limited to H &amp; c2_12 alkylcarbonyl, And n is 0 or 1; and a pharmaceutically acceptable salt thereof. The restriction is that only one of R1'R2, R3, R5, r6 ,, Rb, RC &amp; Rd is linked to the carrier. 58. The pharmaceutical composition according to item 57 of the application, wherein the carrier is a solid-phase carrier. 59- The pharmaceutical composition according to item 57 of the scope of patent application, wherein when n is 0 ′, R1 and R2 are connected, and the carbon to which they are attached, to form 5 to 7 carbon atoms and optionally 1 to Cycloalkyl ring optionally substituted with 3 alkyl groups. 60. The pharmaceutical composition according to Item 57 of the patent application park, wherein when 11 is 1, and R2 is connected, in addition, the carbon atoms to which R21R3 is attached form 5 to 7 carbon atoms and if necessary 丨To a cycloalkyl ring substituted with 3 alkyl groups. 61. The pharmaceutical composition according to item 60 of the patent application park, where 4 is _XR5, where X is -NH- and R5 is cycloalkyl. 62. The pharmaceutical composition according to item 57 of the scope of the patent application, wherein when n is 23- this paper is applicable to Chinese National Standard (CNS) Eighty-fourth Secret (210) &lt; 297 publication) II-I Pack-( Please read the notes on the back before filling in this page.) Order by the China Ministry of Economic Affairs and Economic Affairs Bureau I. Consumer Cooperation. Printed. 4679 A8 B8 C8 DS. Application scope of patent 1 'R and R3 are connected, plus the carbon atoms to which they are attached. To form an n-pinene ring. 63. The pharmaceutical composition according to item 57 of the scope of the patent application, which contains 1% of a pharmaceutically acceptable carrier, and 1-99 ~ 1;% of a carrier containing a 1-thiogalactose derivative, including its Carriers with at least one compound of formula I 'covalently bonded thereto: ReO ^ 〇Rd. R3 R1 R2 (Please read the notes on the back before filling this page) OR3 where R [is selected from the following including hydrogen, alkyl and phenyl; R2 is selected from hydrogen or Cu alkyl; R3 is selected from hydrogen or Ci.6 alkyl ; Or R1 and R2 'or R1 and R3' or R2 and R3, or R1 ·, trans 2 and r3. Can be connected 'plus carbon atoms attached to R1 and / or R2, or R1 and / or R3 to form a ring Alkyl ring; R4 series-XR5 printed by the Central Standards Bureau of the Ministry of Economic Affairs—Industrial and Consumer Cooperatives, where X and R5 form an amine group or an amino acid, selected from the following including glycine, β-alanine, leucine Acid, histidine, tryptophan, and arginine; or X-N—- and R5—H: C ^ .8 alkyl or cycloalkyl; or R4—XCOR6 of which X—NH— and R6 are Cm Alkyl or 2-carboxyphenyl; Y-based sulfur; Ra, Rb, RC, and Rd are each independent and limited to Η and C2-12 alkylcarbonyl-24- Chinese paper standard (CNS) A4 specification (2丨 0X297 male thin 7 46 7 A8 B8 C8 D8 The Ministry of Economic Affairs, China ’s Standard Bureau ’s Consumer Cooperatives printed a patent application base, and η is 0 or 1; and its pharmaceutically acceptable salt. The compound can inhibit toxins and their effects. Binding, or the compound can inhibit the binding of an organism to its cell surface receptor; and the restriction is that only one of R1, R2, R3, r5, r6, Ra, Rb, RiRd is linked to the carrier e team according to the scope of patent application The pharmaceutical composition according to item 63, wherein the toxin is heat-labile enterotoxin or cholera toxin. 65. The pharmaceutical composition according to item 63 of the application, wherein the organism is Vibrio cholerae, or coliform Enterotoxin-producing strain of C. sclerotiorum. 66. The pharmaceutical composition according to item 63 of the patent application, wherein the carrier is a solid phase carrier. 67. The pharmaceutical composition according to item 63 of the patent application, wherein n is 0, R1 and R2 are connected to t ′ and the carbon to which they are attached to form an environmental group having 5 to 7 carbon atoms and optionally substituted by 1 to 3 alkyl groups. 68. Pharmaceuticals according to item 63 of the scope of patent application A composition in which ^ is Bu, R1 and R2 are connected, and carbon atoms attached to R1, R2, and R3 are added to form a ring burner having 5 to 7 broken atoms and optionally substituted by 1 to 3 alkyl groups. Base ring. _Pharmaceuticals under item 68 of the scope of patent application A composition wherein R4 is _XR5 'where X is -NH- and R5 is a cycloalkyl group. 70. A pharmaceutical composition according to item 63 of the scope of the claimed patent, wherein t, R2 and R3 are connected, plus The attached carbon atoms form a positive donation ring. 25-The size of this paper adopts the Chinese National Standard (CNS) 8 4 specifications (210X297 mm) (please read the notes on the back before filling in this education) -Refer to * 1T