AU1633000A - Acetal benzylmaltosides as inhibitors of smooth muscle cell proliferation - Google Patents

Description

WO 00/31096 PCT/US99/27828 -1 ACETAL BENZYLMALTOSIDES AS INHIBITORS OF SMOOTH MUSCLE CELL PROLIFERATION BACKGROUND OF THE INVENTION 5 This invention relates to the use of substituted 4',6'-acetal benzylmaltosides as smooth muscle cell proliferation inhibitors and as therapeutic compositions for treating diseases and conditions which are characterized by excessive smooth muscle proliferation such as restenosis. 10 All forms of vascular reconstruction such as angioplasty and vein bypass procedures effect a response to injury that ultimately leads to smooth muscle cell (SMC) proliferation and subsequently, deposition of profuse amounts of extracellular matrix (Clowes, A. W.; Reidy, M. A. J. Vasc. Surg 1991, 13, 885). 15 These events are also central processes in the pathogenesis of atherosclerosis (Raines E.W.; Ross R. Br. Heart J. 1993, 69 (Supplement), S. 30) as well as transplant arteriosclerosis (Isik, F.F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.; Gordon Am. J. Pathol. 1992, 141, 1139). In the case of restenosis following angioplasty, clinically relevant solutions for controlling SMC proliferation through 20 pharmacological intervention have remained elusive to date (Herrman, J. P. R.; Hermans, W.R.M.; Vos, J.; Serruys P. W. Drugs 1993, 4, 18 and 249). Any successful approach to selective SMC proliferation inhibition must not interfere with endothelial cell repair or the normal proliferation and function of other cells (Weissberg, P.L.; Grainger, D.J.; Shanahan C.M.; Metcalfe, J.C. Cardiovascular 25 Res. 1993, 27, 1191). The glycosaminoglycans heparin and heparan sulfate are endogenous inhibitors of SMC proliferation, yet are able to promote endothelial cell growth (Castellot, J.J. Jr.; Wright, T. C.; Karnovsky, M.J. Seminars in Thrombosis and Hemostasis 1987, 13, 489). However, the full clinical benefits of heparin, heparin 30 fragments, chemically modified heparin, low molecular weight heparins, and other heparin mimicking anionic polysaccharides may be compromised due to other pharmacological liabilities (excessive bleeding arising from anticoagulation effects, in WO 00/31096 PCT/US99/27828 -2 particular) coupled with heterogeneity of the various preparations (Borman, S. Chemical and Engineering News, 1993, June 28, 27). WO 96/14325 discloses acylated benzylglycosides as smooth muscle cell 5 proliferation inhibitors. The compounds of the present invention differ in that the substituents on the carbohydrate backbone are different. Zehavi, U.; Herchman, M. in Carbohyd. Res. 1986, 151, 371, disclosed 4 carboxy-2-nitrobenzyl 4-O-a-D-glucopyranosyl-p-D-glucopyranoside which is attached to a polymer for study as an acceptor in the glycogen synthase reaction. The 10 compounds of the present invention differ in that the substituents on the benzyl groups are different and the use (smooth muscle antiproliferation) is different. Patent numbers US 5,498,775, WO96/14324, and US 5,464,827 describe polyanionic benzylglycosides or cyclodextrins as smooth muscle cell proliferation inhibitors for treating diseases and conditions which are characterized by excessive 15 smooth muscle proliferation. 03-cyclodextrin tetradecasulfate has been described as a smooth muscle cell proliferation inhibitor and as an effective inhibitor of restenosis (Reilly, C.F.; Fujita, T.; McFall, R. C.; Stabilito, I. I.; Wai-se E.; Johnson, R. G. Drug Development Research 1993, 29, 137). US 5019562 discloses anionic derivatives of cyclodextrins for treating pathological conditions associated with 20 undesirable cell or tissue growth. WO 93/09790 discloses antiproliferative polyanionic derivatives of cyclodextrins bearing at least 2 anionic residues per carbohydrate residues. Meinetsberger (EP 312087 A2 and EP 312086 A2) describes the antithrombotic and anticoagulant properties of sulfated bis-aldonic acid amides. US 4431637 discloses polysulfated phenolic glycosides as modulators of the 25 complement system. The compounds of the present invention differ from all of the prior art in that the compounds (a) are benzylglycosylamides which bear no structural resemblance to heparin, sulfated cyclodextrins, or to sulfated lactobionic acid dimers, (b) contain no more than two contiguous sugar residues (disaccharide), (c) are of a defined structure, (d) and are not sulfated. 30 WO 00/31096 PCT/US99/27828 -3 DESCRIPTION OF THE INVENTION This invention provides benzylmaltosides of formula I 7 028 R OO! R R 5 040 OO X

R

6 0 9 R I 5 wherein X is O or S;

R

1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon 10 atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with

R

8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted with R 8 , and thiazolyl substituted with RS;

R

2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 15 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, WO 00/31096 PCT/US99/27828 -4 0 R1 0

JR

11 0~.RO - ~ 0 Ri2 X~ _NRio O% R1o Rio J R 12 S O R - H2 )N o0 R 0

R

1 2 I - 1 oo N S , o o \) N \1k"r .1 _ , N ,or N Rio R10

R

3 , R 4 , R 5 , and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , 5 haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms;

R

7 is hydrogen, methyl, or phenyl;

R

8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN,

-NO

2 , halogen, or -CF3; 10 R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN,

-NO

2 , halogen, -CF 3 , -NHR 3 , -NR 3

R

3 , -NR 3

R

14 , -NHCO 2

R

14 , -NHSO 2

R

14

,

WO 00/31096 PCT/US99/27828 -5 N - \ RN - - ''O Rio - - X Rio0 H R-R H 4 -NH P '-NH

NHR

15 iqlO1 I=11 H

N

, or "1 Rio - NH n

R

10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of 5 the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3;

R

13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 10 carbon atoms, or halogen;

R

1 4 is alkyl of 1-6 carbon atoms;

R

15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16

R

16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; WO 00/31096 PCT/US99/27828 -6 p = 0-6; or a pharmaceutically acceptable salt thereof. Alkyl includes both straight chain as well as branched moieties. Halogen 5 means bromine, chlorine, fluorine, and iodine. When a compound of this invention contains a group that contains the same moiety more than once (i.e., when R 9 is

-NR

3

R

3 ), each of the moieties may be the same or different. Pharmaceutically acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, 10 malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids. Salts may also be formed from organic and inorganic bases, preferably alkali metal salts, for example, sodium, lithium, or potassium. Acid addition salts can be prepared when Y is nitrogen or the 15 compound of formula I contains a basic nitrogen, and base addition salts can typically be prepared when the compound of formula I contains a hydroxyl group. The compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric 20 centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry in Formula I, the present invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof. 25 Preferred compounds of this invention are benzylmaltosides of formula I WO 00/31096 PCT/US99/27828 -7 R x O R 3 0 ! R 4RR O R 8

R

6 0

IR

9 wherein X is 0 or S;

R

1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 5 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with

R

8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted with R 8 , and thiazolyl substituted with RS; 10 R 2 is hydrogen, acyl of 2-6 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, 0 R 1 Rio R1o 7 X~!#?R 1 2 R 1 0 C0 Si.,,s R O R11J 0)R12 KA 2-J -CH 2 nSR 10 0R 1 2 SO2-Rio- CH2 0 0R -R1"__ 2 j- 1 0 '"/ 1l y'" orR12

R

1 3

R

3 , R 4 , R 5 , and R 6 are each, independently, hydrogen, or acyl of 2-7 carbon atoms; 15 R 7 is hydrogen, methyl, or phenyl;

R

8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN,

-NO

2 , halogen, or-CF3; WO 00/31096 PCT/US99/27828 -8

R

9 is hydrogen, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3

R

3 , -NR 3

R

14 , -NHCO 2

R

14 ,

-NHSO

2

R

14 , R14 -NH P -i-NH r

NHR

15 RNo N -N O R1o -o-NrRio , o0 R12 "H ,or . N - R -1-NH n 5

R

10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 10 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3;

R

13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen" -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or halogen; 15 R 14 is alkyl of 1-6 carbon atoms;

R

15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16

R

16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; p = 0-6; 20 or a pharmaceutically acceptable salt thereof.

WO 00/31096 PCT/US99/27828 -9 More preferred compounds of this invention are benzylmaltosides of formula I R 1 OO1 R3oII6 - R 4 0 R X R 8

R

5 0 x

R

6 0 I wherein 5 X is O;

R

1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with 10 R 8 , or pyridyl substituted with R 8 ;

R

2 is hydrogen, acyl of 2-6 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, 10 1 2R i - C H 2 R1 1 lN n R 1 2 O S 2 - R i RR 13 12 R10 .R 1 1 02 ,€,, Q ] k R12 R10 N ~or , /; R11 15 R 3 , R 4 , R 5 , and R 6 are each, independently, hydrogen, or acyl of 2-7 carbon atoms;

R

7 is hydrogen;

R

8 is hydrogen, alkyl of 1-6 carbon atoms, -CN, or halogen;

R

9 is hydrogen, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3

R

3 , -NR 3

R

14 , -NHCO 2

R

14 '

-NHSO

2

R

14

,

WO 00/31096 PCT/US99/27828 - 10 R14 - -NHV'P ' -- NH

NHR

15 O - N N -N k %R10 1H -Rio H 0

R

1 0

R

11

R

10 0 ~ 1 H ,or R12 - NH n

R

10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 5 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3;

R

13 is hydrogen, alkyl of 1-6 carbon atoms, halogen, or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 10 carbon atoms, alkoxy of 1-6 carbon atoms, or halogen;

R

14 is alkyl of 1-6 carbon atoms;

R

15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16

R

16 is alkyl of 1-6 carbon atoms, or fluorenyl; n=0-3; 15 p = 0-6; or a pharmaceutically acceptable salt thereof. Specifically preferred compounds of this invention are: N- { 2-Chloro-5-[(4',6'-O-ethylidene)-p-D-maltosyloxymethyl]-phenyl }-acetamide or 20 a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 11 (R)-N-[5-[[[6-O-Benzoyl-4-O-(4,6-O-ethyidene-a-D-glucopyranosyl)-p-D glucopyranosyl]oxy]methyl]-2-chlorophenyl]acetamide or a pharmaceutically acceptable salt thereof; 5 (R)-N-[2-Chloro-5-[[[2,3-di- O-acetyl-6- O-benzoyl-4- O-(2,3-di-O-acetyl-4,6- O ethylidene-a-D-glucopyranosyl)-p-D-glucopyranosyl]oxy]methyl] phenyl]acetamide or a pharmaceutically acceptable salt thereof; 10 N- { 2-Chloro-5-[(4',6'-O-propylidene-p-D-maltosyl)-oxy-methyl]-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6- O-Benzoyl-4',6' - O-propylidene- -D-maltosyl)-oxy-methyl]-2-chloro phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 15 N-(5- { [4',6'-O-Benzylidene-6-O-(4-toluenesulfonyl)- p-D-maltosyl]-oxy-methyl }-2 chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; N-(5- { [2,3,2',3'-Tetra- O-acetyl-4',6' - O-benzylidene-6- O-(4-toluenesulfonyl)-p-D 20 maltosyl]-oxy-methyl}-2-chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6-O-Benzyl-4',6'-O-benzylidene- p-D-maltosyl)-oxy-methyl]-2-chloro phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 25 N- ({5-[(6-O-Benzyl-4',6'-O-ethylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl

}

acetamide or a pharmaceutically acceptable salt thereof; N-(2-Chloro-5- { [4',6'-O-(4-nitro)-benzylidene-0-D-maltosyl]-oxy-methyl }-phenyl) 30 acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/UIS99/27828 - 12 N-(5- { [6-O-Benzoyl-4',6'-O-(4-nitro)-benzylidene-p-D-maltosyl]-oxy-methyl }-2 chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; N-{ 2-Chloro-5-[(4',6'-O-(4-chloro)-benzylidene-p-D-maltosyl)-oxy-methyl] 5 phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6-0O-Benzoyl-4',6'-O-(4-chloro)-benzylidene-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 10 N- { 2-Chloro-5-[(4',6'- O-isobutylidene- p-D-maltosyl)-oxy-methyl]-phenyl } acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6- O-Benzoyl-4',6'-O-isobutylidene- p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 15 N- { 5- [(4',6'- O-((1R)-2-Phenyl-ethylidene)-p-D-maltosyloxy)-methyl]-2-chloro phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N-{5-[(6-O-Benzoyl-4',6'-O-((1R)-2-phenyl-ethylidene)-p-D-maltosyloxy)-methyl] 20 2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; N- { 2-Chloro-5-[(4',6'- O-(( 1R)-3-cyano-propylidene)-p-D-maltosyloxy)-methyl] phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 25 N- {5-{ [6-O-Benzoyl-4',6'-O-((1R)-3-cyanopropylidene)-p-D-maltosyloxy]-methyl} 2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N- { 2-Chloro-5-[(4',6'-O-(( 1R)-3-ethoxy-propylidene)-p-D-maltosyloxy)-methyl] phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 30 N-f 5-f{ [6-O-Benzoyl-4',6'-O-((1R)-3-ethoxypropylidene)-p-D-maltosyloxy]-methyl } 2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -13 N-(2-Chloro-5- { [4',6'-O-(4-pyridinemethylidene)- 1-D-maltosyl]-oxy-methyl } phenyl)-acetamide or a pharmaceutically acceptable salt thereof; 5 Benzoic acid 6-(3-acetylamino-4-chloro-benzoyloxy)-3-(7,8-dihydroxy-2-pyridin-4 yl-hexahydro-pyrano [3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2 ylmethyl ester or a pharmaceutically acceptable salt thereof; N- { 5-[(4',6'-O-Benzylidene-1-D-maltosyloxy)-methyl]-2-chloro-phenyl } -acetamide 10 or a pharmaceutically acceptable salt thereof; N- { 5-[(4',6'-O-Benzylidene-2,2',3,3',6-penta-O-acetyl-3-D-maltosyl-oxy)-methyl]-2 chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 15 N-{5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl-oxy)-methyl]-2-chloro phenyl}-acetamide or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-6-0O-benzoyl-4-O-[2,3-di-O-acetyl-4,6-O (phenylmethylene)-a-D-glucopyranoysl]-p-glucopyranosyl]-oxy]methyl] 20 phenyl]acetamide or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[6-O-(5-methoxy-1,5-dioxopentyl)-4-0-[4,6-0 (phenylmethylene)-a-D-glucopyranoysl]-p-D-glucopyranosyl]oxy]methyl] phenyl]acetamide or a pharmaceutically acceptable salt thereof; 25 4-Chloro-3-nitro-benzyl-4',6'-O-benyzlidene--D-maltoside or a pharmaceutically acceptable salt thereof; 4-Chloro-3-nitro-benzyl-6-O-benzoyl-4',6'-O-benyzlidene-p-D-maltoside or a 30 pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 14 (R)-(4-Chloro-3-nitrophenyl)methyl-2,3-di-O-acetyl-6- O-benzoyl-4- O-[2,3-di- O acetyl-4,6-O-(phenylmethylene)-a-D-glucopyranosyl]-p-D-glucopyranoside or a pharmaceutically acceptable salt thereof; 5 Nicotinic acid 6-(4-chloro-3-nitro-benzyloxy)-3-(7,8-dihydroxy-2-phenyl-hexahydro pyrano[3,2-d][1,3]dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; (R)-(4-Chloro-3-nitrophenyl)methyl 4-[2,3-di-O-acetyl-4,6-O-(phenylmethylene)-a 10 D-glucopyranosyl]-p-D-glucopyranoside 2,3-diacetate 6-(3-pyridinecarboxylate) or a pharmaceutically acceptable salt thereof; 4-Methoxy-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro 15 pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 4-Methoxy-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 diacetoxy-2-phenyl-hexahydro-pyrano [3,2-d] [1,3] dioxin-6-yloxy)-tetrahydro-pyran 2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 20 4-Chloro-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano [3,2-d] [1,3] dioxin- 6-yloxy)-4,5-dihydroxy-tetrahydro pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 25 4-Chloro-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-tetrahydro-pyran 2-ylmethyl ester or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[6-0O -(4-chloro-3-nitrobenzoyl)-4- O-[4,60-(phenylmethylene) 30 a-D-glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -15 N- { 5-[(2,2',3,-Tri-O -Acetyl-6-0O -(4-chloro-3-nitrobenzoyl)-4',6'-O-(benzylidene) p-D-maltosyl)-oxymethyl]-2-chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; 5 (R)-N-[2-Chloro-5-[[[6- 0 -(4-cyanobenzoyl)-4-O-[4,60-(phenylmethylene)--D glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[6-0 -(4-nitrobenzoyl)-4-O-[4,60-(phenylmethylene)-a-D 10 glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[6-0O -(3-trifluoromethylbenzoyl)-4-O-[4,60 (phenylmethylene)-x-D-glucopyranosyl]- p-D-glucopyranosyl] oxy] 15 methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; N-{ 5-[(4',6'-O-Benzylidene-6-O-(2-iodo)-benzoyl-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; 20 N- {5-[(4',6'-O-Benzylidene-6-O-(3-iodo)-benzoyl-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(4',6'-O-Benzylidene-6-(4-iodo-benzoyl)-oxy- -D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 25 (R)-N-[-2-Chloro-5-[[[6-O-(phenylacetyl)-4-O-[4,6-O-(phenylmethylene)-a-D glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; 30 (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-4-O-[2,3-di-O-acetyl-4,6-O-(phenyl methylene)-a-D-glucopyranosyl]-6-O-(phenylacetyl)-p-D-glucopyranosyl] oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -16 N- { 5-[(4',6'- O-Benzylidene-6- O-phenyl-ethyl-carboxyl-p-D-maltosyl)-oxy-methyl] 2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 5 N- { 5-[(4',6'-O-Benzylidene-6- O-phenyl-propyl-carboxyl-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; Diphenyl-acetic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro 10 pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; Diphenyl-acetic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6-yloxy)-tetrahydro-pyran 2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 15 (3,4-Dimethoxy-phenyl)-acetic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 20 (3,4-Dimethoxy-phenyl)-acetic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro benzyloxy)-3-(7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6-yloxy) tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; Nicotinic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2-phenyl 25 hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2 ylmethyl ester or a pharmaceutically acceptable salt thereof; Nicotinic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-diacetoxy 2-phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-tetrahydro-pyran-2-ylmethyl 30 ester or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -17 (R)-N-[5-[[[6-O-(4-Benzoylbenzoyl)-4-O-[4,6-O-(phenylmethylene)-a-D glucopyranosyl]-p3-D-glucopyranosyl]oxy]methyl]-2-chlorophenyl]acetamide or a pharmaceutically acceptable salt thereof; 5 N- { 5-[(4',6'-O-Benzylidene-p3-maltosyl)-oxy-methyl]-2-methyl-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; N-Acetyl-{ 5-[(2,2',3,3',6-penta-O-acetyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy methyl]-2-methyl-phenyl}acetamide or a pharmaceutically acceptable salt thereof; 10 N-(5- { [4',6' - O-Benzylidene-6- O-(4-toluenesulfonyl)- p3-D-maltosyl]-oxy-methyl }-2 methyl-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(4',6'- O-Benzylidene-6-0O-phenyl- -D-maltosyl)-oxy-methyl]-2-chloro 15 phenyl}-acetamide or a pharmaceutically acceptable salt thereof; (R)-N-[2-Chloro-5-[[[4-O-[4',6'-O-(phenylmethylene)-oa-D-glucopyranosyl]-p3-D glucopyranosyl]oxy]methyl] phenyl]-3-pyridinecarboxamide or a pharmaceutically acceptable salt thereof; 20 (R)-N-[5-[[[6-0-Benzoyl-4-0-[4' ,6'-O-(phenylmethylene)-a-D-glucopyranosyl]-3-D glucopyranosyl]oxy]methyl]-2-chlorophenyl]-3-pyridinecarboxamide or a pharmaceutically acceptable salt thereof; 25 Furan-2-carboxylic acid {5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-amide or a pharmaceutically acceptable salt thereof; Furan-2-carboxylic acid { 5-[(6-O-benzoyl-4',6'-O-benzylidene-3-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-amide or a pharmaceutically acceptable salt thereof; 30 N- { 2-Chloro-5-[(4',6'- O-benzylidene- 1-D-maltosyl)-oxy-methyl]-phenyl }-pent-4 enamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 18 N- { 2-Chloro-5-[(6-O-benzoyl-4',6'-O-benzilidene-p-D-maltosyl)-oxy-methyl] phenyl }-pent-4-enamide or a pharmaceutically acceptable salt thereof; 5 5-(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl-2-chloro phenylamine or a pharmaceutically acceptable salt thereof; (4-Chloro)-benzyl-4',6'-O-benzylidene-p-D-maltoside or a pharmaceutically acceptable salt thereof; 10 Benzoic acid 1-O-(4-chloro)-benzyl-4',6'-O-benzylidene-6-deoxy-p-D-malto-6-yl ester or a pharmaceutically acceptable salt thereof; 4-Benzoyl-N- {5-[(4',6'- O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl } 15 benzamide or a pharmaceutically acceptable salt thereof; 4-Benzoyl-N- { 5-[(6-benzoyl-oxy-4',6' - O-benzylidene- p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-benzoic acid amide or a pharmaceutically acceptable salt thereof; 20 4-Benzoyl-N- { 5-[(4',6'-O-benzylidene-6-O-(2-iodo)-benzoyl-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-benzamide or a pharmaceutically acceptable salt thereof; 4-Benzoyl-N- { 5-[(4',6'- O-benzylidene-6- O-(3-iodo-benzoyl)-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-benzamide or a pharmaceutically acceptable salt thereof; 25 4-Benzoyl-N- {(5-[(4',6'-O-benzylidene-6-(4-iodo-benzoyl)-oxy- p-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-benzoic acid amide or a pharmaceutically acceptable salt thereof; 30 (1- { 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl carbamoyl}ethyl)-carbamic acid 9H-fluoren-9ylmethyl ester or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -19 N-(9H-Fluoren-9ylmethoxycarbonyl)-N'- { 5- [(6-O-benzoyl-4',6'-O-benzylidene- p-D maltosyl)-oxy-methyl]-2-chloro-phenyl }-L-alaninamide or a pharmaceutically acceptable salt thereof; 5 N'- { 5-[(6-0-benzoyl-4',6'-O-benzylidene- p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-L-alaninamide or a pharmaceutically acceptable salt thereof; N-{ 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxymethyl]-2-chloro-phenyl }-N-methyl 10 acetamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6-O-Benzoyl-4',6'- O-benzylidene- p-D-maltosyl)-oxymethyl]-2-chloro phenyl}-N-methyl-acetamide or a pharmaceutically acceptable salt thereof; 15 N- { 5-[(4',6'- O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl }-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; N- {5-[(6- O-Benzoyl-4',6' -O-benzylidene- p-D-maltosyl)-oxy-methyl] -2-chloro phenyl}-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; 20 N-{ 5-[(6-O-(3-Benzyl- 1l-oxo-propyl)-4',6'-O-benzylidene-f3-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; 25 N- { 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl

}

methanesulfonamide or a pharmaceutically acceptable salt thereof; N- { 5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-cyano phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 30 N- { 5-[(6- O-Benzoyl-4',6' -O-benzylidene- p -D-maltosyl)-oxy-methyl]-2-methyl phenyl }-acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 20 6-[-6-( 4 -Chloro-3-nitro-benzylsulfanyl)-4,5-dihydroxy-2-hydroxymethyl-tetrahydro pyran-3-yloxy]-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol or a pharmaceutically acceptable salt thereof; 5 (4-Chloro-3-nitro-benzyl) 6-O-benzoyl-4',6'-0- benzoyl-4',6',-O-benzylidene-1 thio-p-D-maltoside or a pharmaceutically acceptable salt thereof. 10 The compounds of this invention were be prepared according to the following schemes from commercially available starting materials or starting materials which can be prepared using literature procedures. This scheme shows the preparation of representative compounds of this invention. 15 Acetobromomaltose 1 is coupled with a benzyl alcohol 2 in the presence of a catalyst such as a mercuric bromide, mercuric cyanide, silver triflate, or silver perchlorate in an aprotic solvent such as acetonitrile, dichloromethane, ether, toluene or nitromethane at temperatures ranging from -40 oC to reflux to yield glycoside 3 (Scheme 1). This glycosidation can also be accomplished using Schmidt's 20 trichloroacetimidate coupling with zinc bromide in a solvent such as dichloromethane. Reduction of the nitro group of 3 can be accomplished with a reducing agent such as stannous chloride in a polar aprotic solvent such as ethyl acetate at ambient temperature to reflux to afford an anilino compound 4. Coupling of 4 with an acid chloride can be completed in the presence of an amine base such as 25 triethylamine or diisopropylethylamine or using a stronger base such as sodium hydride (for sterically hindered systems) in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures ranging from 0 oC to ambient temperature to yield the target compound 5. The peracetylated compound 5 can be converted to the heptahydroxy compound 6 with catalytic sodium methoxide in 30 methanol or aqueous sodium hydroxide in methanol at temperatures ranging from ambient temperature to reflux.

WO 00/31096 PCT/US99/27828 -21 As illustrated in Scheme 2, an acetal (7) was formed at the C-4',6' positions of the disaccharide of heptahydroxy compound 6 using an appropriate aldehyde dimethyl or diethyl acetal and an acid source such as p-toluenesulfonic acid monohydrate or camphorsulfonic acid in a polar solvent such as N,N 5 dimethylformamide at 60 oC. In difficult cases, an aldehyde and sulfuric acid can be used in DMF at higher temperatures to obtain the product acetal. At this point, the 6 position primary alcohol was selectively acylated using an acid chloride in a 1:1 mixture of tetrahydrofuran and the hindered base 2,4,6-collidine at -40 oC initially to ambient temperature overnight to generate compound 8. The remaining four 10 secondary alcohols of the disaccharide can then be protected with acetic anhydride and triethylamine in a solvent such as dichloromethane to afford the peracetylated compound 9. On the other hand, acetal 7 can first be converted to a tosylate using tosyl chloride and pyridine in a solvent such as dichloromethane (Scheme 3); the resulting 15 intermediate is then peracetylated as mentioned above to generate compound 10. Through overall displacement of the 6-position tosylate (alcohol formation with sodium formate followed by ether formation with benzyl 2,2,2-trichloroacetimidate), an ether linkage is incorporated at this site on the molecule. The benzylidene acetal is then removed under strongly acidic conditions such as 1M ethereal HC1 to afford 20 compound 11. A new acetal is then formed at the C-4',6' positions using the conditions mentioned previously or just an aldehyde and the acid source in benzene at elevated temperature (60 oC). Finally, the four secondary acetates are removed with catalytic sodium methoxide in methanol or aqueous sodium hydroxide in methanol at temperatures ranging from ambient temperature to reflux to obtain the hydroxy 25 compound 12.

WO 00/31096 PCT/US99/27828 - 22 Scheme 1 glycosidation

A

c AcO A AcO 0 A Ac AAcO---+ ,OC AcO NO 2 32 reduction oAc AcO O\ AcO Ac AcO ci A AcO N 2 4 N acylation Ac AcO 0 Aco Ac AcO 0 ~A O - fci 5 AcO HN I hydrolysis HO c HH OH O A Oco . _"A 5 Ac HN"-

-

WO 00/31096 PCT/US99/27828 - 23 If R, = Bz, then: Scheme 2 H HO o HO HO OH c 6 HO HO HN 0C4',6'-acetal formation HO O CI 7 HO HN C-6 acylation HO O C 8 HO HN 4 -peracetylation R 1 R R- ci RO R 2O O 0 ~ 8RHO HN-< 5 If R2 = Bn, then: WO 00/31096 PCT/US99/27828 - 24 4 Scheme 3 7~ HOX.

H O H HO HN-O 1) tosylation 2) peracetylation R4 OCH 3 O tAOOC AcO AcO-OC... I 10 AcOHN 1) ether formation 2) acetal removal H Y HO A AcO R 2 AcO A O O C AcO HN 11 1) new C-4',6'-acetal formation 2) hydrolysis R1 4 R3 R0 O

R

3 0 12 WO 00/31096 PCT/US99/27828 - 25 The compounds of this invention are useful as antiproliferative agents. The following procedures show the evaluation of representative compounds of this invention in standard pharmacological test procedure which measured ability of the evaluated compound to inhibit smooth muscle cell proliferation. 5 Effects of Compounds on Cell Proliferation Using 3H Thvmidine Incorporation Human and porcine smooth muscle cells were tested in early passage (generally passage 3 - 7) at sub-confluent conditions. Cultures were grown in 16 mm (24 well) multi-well culture dishes in medium 199 supplemented with 10% fetal bovine serum 10 and 2% antibiotic / antimycotic. At sub-confluence, the cells were placed in a defined serum free medium (AIM-V; Gibco) for 24 - 48 h prior to initiating the experimental protocol. Although compounds were found to be more effective with longer pre-incubations, in general, the procedures were initiated with the addition of compound, 3 H thymidine 15 and serum / growth factor to serum deprived synchronized cells and results are reported accordingly. Compounds were added to each well at 50 fold dilution (20 pL / well) and the plates were incubated for 24 - 36 h at 37 oC in 5% CO 2 . Compounds were initially dissolved in 50% ethanol and serially diluted into media. Compounds were routinely 20 evaluated at concentrations from 1 to 100 pM. As a control, grade II porcine intestinal mucosal heparin (sodium salt) was routinely evaluated in all cell preparations at concentrations from 0.1 to 100 pg/mL. At the completion of the test procedure, plates were placed on ice, washed three times with ice cold phosphate buffered saline (PBS) and incubated in ice cold 10% 25 trichloroacetic acid (TCA) got 30 min to remove acid soluble proteins. Solution was transferred to scintillation vials containing 0.4 N HC1 (500 pL/ vial to neutralize NaOH) and each well was rinsed two times with water (500 pL) for a total volume of 2 mL / vial. Data was obtained, in triplicate, for both control and experimental samples. Control 30 (100%) data was obtained from maximally stimulated cells, as the result of growth factor or serum stimulation. Experimental data was obtained from cells maximally WO 00/31096 PCT/US99/27828 - 26 stimulated with growth factor or serum and treated with compound. Data are expressed as an IC 50 or percent inhibition in Table I below. Table 1. Porcine Smooth Muscle Cell Compound of Example Antiproliferation IC50 1 32% @ 100 JM 2 0.103 pM 3 2.92 pM 4 16% @ 50 pM 5 0.037 pM 6 0.133 pM 7 0.088 pM 8 0.001 pM 9 0.083 pM 10 19.2 pM 11 0.003 pM 12 29.4 pM 13 0.023 pM 15 0.003 pM 16 16.3 pM 17 0.035 pM 18 43% @ 50 ipM 19 0.001 pM 20 48% @ 50 pM 21 0.062 pM 22 5.53 pM 23 0.003 pM 24 6.60 pM 25 0.700 pM 26 0.010-0.030 pM 27 0.070 pM 28 0.400 pM 29 44.1 pM 30 0.351 pM 31 0.380 pM 32 0.405 pM 33 0.312 pM 34 0.061 pM 35 0.851 pM 36 0.089 pM 37 0.588 pM 38 0.187 pM 39 2.53 pM WO 00/31096 PCT/US99/27828 - 27 Table 1 (Continued) Porcine Smooth Muscle Cell Compound of Example Antiproliferation IC50 40 0.092 pM 41 0.273 pM 42 0.027 pM 43 0.008 pM 44 0.062 pM 45 6.44 pM 46 0.032 pM 47 0.078 pM 48 0.007 pM 49 0.104 pM 50 0.084 pM 51 0.354 pM 52 0.048 pM 53 0.266 pM 54 0.211 pM 55 0.304 pM 56 0.530 pM 57 8.90 pM 58 0.600 pM 59 0.490 tpM 60 0.038 pM 61 13.7 pM 62 0.023 pM 63 7.73 pM 64 0.050 pM 65 17.8 pM 66 0.180 pM 67 1.29 pM 68 25.3 pM 69 1.53 pM 70 9.94 pM 71 0.050 pM 72 0.016 pM 73 0.132 pM 74 1.22 pM 75 4.69 pM 76 0.156 pM 77 0.081 pM 78 8% @ 50 pM 79 2.36 pM WO 00/31096 PCT/US99/27828 - 28 Table 1 (Continued) 80 7.57 pM 81 0.014 pM 82 0.352 pM 83 18% @ 50 pM 84 0.250 pM 85 0.418 pM 86 16.3 pM 87 0.031 pM 5 The compounds of this invention are useful in treating or inhibiting diseases which are characterized by excessive smooth muscle cell proliferation (smooth muscle cell hyperproliferation). The compounds are particularly useful in treating hyperproliferative vascular diseases which are characterized by smooth muscle cell 10 hyperproliferation, such as restenosis, which most frequently arises from vascular reconstructive surgery and transplantation, for example, balloon angioplasty, vascular graft surgery, coronary artery bypass surgery, and heart transplantation. Other disease states in which there is unwanted "cellular" vascular proliferation include hypertension, asthma, and congestive heart failure. The compounds of this invention 15 are also useful as inhibitors of angiogenesis. Angiogenesis (neovascularization), the process by which new capillaries are formed, is of principal importance for a number of pathological events including chronic inflammation and malignant processes. The compounds of this invention are therefore useful as antineoplastic agents. 20 The compounds of this invention can be formulated neat or with a pharmaceutical carrier for administration, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard pharmacological practice. The pharmaceutical carrier may be solid or liquid. 25 A solid carrier can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents; it can also be an WO 00/31096 PCTIUS99/27828 - 29 encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets 5 preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. Liquid carriers are used in preparing solutions, suspensions, emulsions, 10 syrups, elixirs and pressurized compositions. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, 15 thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, lethicins, and oils (e.g. 20 fractionated coconut oil and arachis oil). For parenteral administration, the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are useful in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant. 25 Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. The compounds of this invention can also be administered orally either in liquid or solid composition form. 30 The compounds of this invention may be administered rectally or vaginally in the form of a conventional suppository. For administration by intranasal or intrabronchial inhalation or insufflation, the compounds of this invention may be formulated into an aqueous or partially aqueous solution, which can then be utilized in the form of an aerosol. The compounds of this invention may also be administered 35 transdermally through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non toxic to the skin, and allows WO 00/31096 PCT/US99/27828 - 30 delivery of the agent for systemic absorption into the blood stream via the skin. The carrier may take any number of forms such as creams and ointments, pastes, gels, and occlusive devices. The creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of 5 absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable. A variety of occlusive devices may be used to release the active ingredient into the blood stream such as a semipermeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient. Other occlusive devices are 10 known in the literature. The dosage requirements vary with the particular compositions employed, the route of administration, the severity of the symptoms presented and the particular subject being treated. Based on the results obtained in the standard pharmacological test procedures, projected daily dosages of active compound would be 0.1 to 10 15 mg/kg administered parenterally (intravenous preferred), with projected daily oral dosage being approximately ten-fold higher. Anticipated intravenous administration would last for approximately 5-30 days following acute vascular injury (i.e., balloon angioplasty or transplantation) and for a longer duration for the treatment of chronic disorders. Treatment will generally be initiated with small dosages less than the 20 optimum dose of the compound. Thereafter the dosage is increased until the optimum effect under the circumstances is reached; precise dosages for oral, parenteral, nasal, or intrabronchial administration will be determined by the administering physician based on experience with the individual subject treated. Preferably, the pharmaceutical composition is in unit dosage form, e.g. as tablets or 25 capsules. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example, packaged powders, vials, ampoules, pre filled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package 30 form.

WO 00/31096 PCT/US99/27828 -31 The following provides the preparation of representative compounds of this invention. Example 1 5 N- {2-Chloro-5-[(4'.6'-O-ethvlidene)--D-maltosyloxvmethvll-phenv1 -acetamide step 1 4-Chloro-3-nitro-benzyl- P-D-maltoside heptaacetate To a stirred solution of 4-chloro-3-nitrobenzyl alcohol (6.70 g, 35.7 mmol) and HgBr, (14.2 g, 39.3 mmol) in freshly distilled CH 3 CN (239 mL) was added in 10 one portion Hg(CN) 2 (9.02 g, 35.7 mmol). After 0.5 h, acetobromomaltose (25.0 g, 35.7 mmol) was added, and the mixture stirred for 18 h at rt. The reaction was then quenched with a mixture of H 2 0:brine (1:1, 100 mL) and extracted with 10%

CH

2 C1 2 :EtOAc. The combined organic extracts were dried (MgSO 4 ) and concentrated. Purification by flash chromatography (10:90 to 80:20 EtOAc:petroleum ether 15 gradient) gave 51.9 g (90%) of the title compound as a glassy oil which was recrystallized from Et20:petroleum ether to afford a glassy white solid, mp 107-111 0 C; 'H NMR (CDCl 3 ) 6 2.00 (s, 3H), 2.02 (s, 3H), 2.03, (s, 3H), 2.04 (s, 6H), 2.11 (s, 3H), 2.15 (s, 3H), 3.70 (ddd, J = 2.9, 4.2, 9.7 Hz, 1H), 3.94-3.98 (m, 1H), 4.01-4.07 (m, 2H), 4.20-4.28 (m, 2H), 4.54 (dd, J = 2.9, 12.3 Hz, 1H), 4.63-4.68 (m, 2H), 4.84 20 4.94 (m, 3H), 5.06 (t, J = 10.1 Hz, 1H), 5.26 (t, J = 9.2 Hz, 1H), 5.36 (dd, J = 9.7, 10.3 Hz, 1H), 5.42 (d, J = 4.2 Hz, 1H), 7.43 (dd, J = 2.2, 8.3 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H); IR (KBr) 3450, 2950, 1755, 1550, 1375, 1230 and 1050 cm'; mass spectrum [(+) ESI], m/z 823/825 (M + NH4+), 828/830 (M + Na)*; Anal. Calcd. for C 33

H

4 0 C1NO 2 0 : C, 49.17; H, 5.00; N, 1.74, Found: C, 49.16; H, 25 4.88; N, 1.71. step 2 2-Chloro-5-(hepta-O-acetyl--D-maltosyl-oxymethyl)-phenylamine A solution containing 4-chloro-3-nitro-benzyl- P3-D-maltoside heptaacetate 30 (19.3 g, 23.9 mmol) and tin (II) chloride dihydrate (37.7 g, 167 mmol) in EtOAc (479 mL) was refluxed for 2 h. The reaction was cooled to rt, carefully quenched with sat. aq. NaHCO, (until basic), diluted with EtOAc (250 mL), stirred for 0.5 h and filtered.

WO 00/31096 PCT/US99/27828 - 32 The biphasic filtrate was separated and the aqueous phase extracted with EtOAc. The combined organic extracts were dried (Na 2

SO

4 ) and concentrated. Purification by flash chromatography (0 to 12% acetone/CHC1 3 gradient) gave 17.8 g (96%) 2 Chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenylamine as a glassy solid, 5 mp 78-79 oC; 1 H NMR (CDC1 3 ) 8 2.00 (s, 9H), 2.026 (s, 3H), 2.032 (s, 3H), 2.11 (s, 3H), 2.16 (s 3H), 3.00-5.00 (bs, 2H), 3.64-3.68 (m, 1H), 3.97 (ddd, J = 2.4, 4.2, 10.1 Hz, 1H), 4.02-4.07 (m, 2H), 4.24 (dd, J = 2.2, 3.7, 1H), 4.27 (dd, J = 2.6, 4.0 Hz, 1H), 4.50-4.57 (m, 3H), 4.74 (d, J = 12.1 Hz, 1H), 4.83-4.90 (m, 2H), 5.05 (t, J = 10.1 Hz, 1H), 5.22 (t, J = 9.2 Hz, 1H), 5.35 (dd, J = 9.7, 10.5 Hz, 1H), 5.42 (d, J = 10 4.0 Hz, 1H), 6.62 (dd, J = 2.0, 8.1 Hz, 1H), 6.76 (d, J = 2.0 Hz, 1H), 7.21 (d, J = 8.1, 1H); IR (KBr) 3450, 3350, 2950, 1755, 1650, 1425, 1375, 1230 and 1050 cm"; mass spectrum [(+) ESI], m/z 776/778 (M + H)+, 798/800 (M + Na)+; Anal. Calcd. for

C

3 3

H

4 C1N0 1 8 : C, 51.07; H, 5.45; N, 1.80, Found: C, 50.94; H, 5.52; N, 1.60. 15 step 3 N-[2-Chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenyl]-acetamide To a stirred solution of 2-chloro-5-(hepta-O-acetyl-p3-D-maltosyl-oxymethyl) phenylamine (20.6 g, 26.5 mmol) and triethylamine (8.13 mL, 58.3 mmol) in THF (265 mL) at 0 oC was added dropwise acetyl chloride (2.26 mL, 31.8 mmol). After 20 0.5 h at this temperature, it was warmed to rt and stirred an additional 6 h. At this point, the reaction was concentrated and taken up in EtOAc (700 mL). This organic solution was washed with 1 N HC1 (70 mL), sat. aq. NaHCO 3 (70 mL), and brine (70 mL) and then dried (MgSO 4 ). After concentration, the residue was purified by flash chromatography (20:80 to 100:0 EtOAc:petroleum ether gradient) to afford the 25 product (16.2 g, 75%) as a glassy solid, mp 84-86 oC; 1 H NMR (CDC1 3 ) 8 2.00 (s, 6H), 2.020 (s, 3H), 2.027 (s, 3H), 2.03 (s, 3H), 2.11 (s, 3H), 2.16 (s, 3H), 2.24 (s, 3H), 3.66-3.69 (m, 1H), 3.94-3.98 (m, 1H), 4.00-4.06 (m, 2H), 4.22-4.28 (m, 2H), 4.50-4.61 (m, 3H), 4.80-4.91 (m, 3H), 5.05 (t, J = 10.1 Hz, 1H), 5.22 (t, J = 9.2 Hz, 1H), 5.35 (dd, J = 9.4, 10.5 Hz, 1H), 5.41 (d, J = 4.0 Hz, 1H), 6.99 (dd, J = 2.0, 8.1 30 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.62 (s, 1H), 8.32 (s, 1H); IR (KBr) 3400, 2950, 1750, 1690, 1600, 1540, 1425, 1375, 1230 and 1050 cm'; mass spectrum [(+) ESI], WO 00/31096 PCT/US99/27828 - 33 m/z 818/820 (M + H)+, 840 (M + Na)'; Anal. Calcd. for C 3 5

H

44 C1NO 1 9 : C, 51.38; H, 5.42; N, 1.71, Found: C, 51.03; H, 5.36; N, 1.59. step 4 5 N-[2-Chloro-5-(P-D-maltosyl-oxymethyl)-phenyl]-acetamide A solution containing N-[2-chloro-5-(hepta-O-acetyl- p-D-maltosyl oxymethyl)-phenyl]-acetamide (0.945 g, 1.12 mmol) and 25 weight % NaOMe in MeOH (19.2 pL, 0.336 mmol) in MeOH (27.6 ml) was refluxed for 2.5 h. The reaction was cooled to room temperature and concentrated, and the resulting residue 10 was triturated with Et 2 O to afford the product (0.583 g, 99%) as a foam; 'H NMR (DMSO-d 6 ) a 2.07 (s, 3H), 3.03-3.16 (m 2H), 3.19-3.49 (m, 7H), 3.55-3.62 (m, 2H), 3.67-3.73 (m, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.33-5.76 (bs, 7H), 4.67 (ABq, J = 12.5 Hz, A5 = 0.22, 2H), 5.01 (d, J = 3.7 Hz, 1H), 7.21 (dd, J = 1.8, 8.1 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 1.5 Hz, 1H), 9.33-9.69 (bs, 1H); IR (KBr) 3400, 2900, 15 1680, 1600, 1540, 1430, 1375, 1310, 1150 and 1035 cm', mass spectrum [(+) ESI], m/z 524/526 (M + H)+, 546 (M + Na)*; Anal. Calcd. for C 2 1

H

3 0 C1NO 1 2 1.0 MeOH: C, 47.53; H, 6.16; N, 2.52. Found: C, 47.94; H, 6.34; N, 2.42. step 5 20 N-{2-Chloro-5-[(4',6'-O-ethylidene)-p-D-maltosyloxymethyl]-phenyl}-acetamide To a stirred solution of N-[2-chloro-5-(1-D-maltosyl-oxymethyl)-phenyl] acetamide (0.500 g, 0.954 mmol) in DMF (12.5 mL) at rt was added acetaldehyde dimethyl acetal (0.202 mL, 1.91 mmol) dropwise followed by TsOH-H 2 O (0.0907 g, 0.477 mmol). The reaction mixture was heated to 60 oC for 6 h and then quenched 25 with K 2

CO

3 (0.0659 g, 0.477 mmol) with an additional 0.5 h heating at this temperature. At this point, the solution was filtered hot, and the solvent was distilled off using the high vac. The residue was purified by flash chromatography (80:2:1 EtOAc:EtOH:H,0) to afford the product (0.323 g, 62%) as an off-white powder, mp 144-146 oC; 'H NMR (DMSO-d) 8 1.22 (d, J = 5.1 Hz, 3H), 2.07 (s, 3H), 3.05-3.11 30 (m, 1H), 3.11 (t, J = 9.4 Hz, 1H), 3.25-3.37 (m, 3), 3.39-3.58 (m, 5H), 3.65-3.71 (m, 1H), 3.92 (dd, J = 4.8, 9.9 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.65 (t, J = 5.7 Hz, 1H), 4.67 (ABq, J = 12.3 Hz, A8 = 0.22, 2H), 4.69 (dd, J = 4.8, 9.9 Hz, 1H), 5.09 (d, J = WO 00/31096 PCT/US99/27828 - 34 4.0 Hz, 1H), 5.23 (t, J = 5.7 Hz, 2H), 5.47 (d, J = 3.5 Hz, 1H), 5.57 (d, J = 6.6 Hz, 1H), 7.22 (dd, J = 1.8, 8.3 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3400, 2910, 2880, 1675, 1600, 1535, 1450, 1420, 1375, 1310, 1150, 1120, 1060, and 1020 cm'; mass spectrum [(+) FAB], m/z 550/552 (M + H)', 5 572/574 (M + Na); Anal. Calcd. for C 23

H

3 2 C1NO12 1.0 H20: C, 48.64; H, 6.03; N, 2.47, Found: C, 48.55; H, 5.90; N, 2.41. Example 2 (R)-N- [5-[[[6-O-Benzovl-4-O-(4.6-O-ethvy1idene-o-D- glucopvranos1)-3-D 10 2lucopvranosyl] oxy]lmethyll]-2-chlorophenv1]acetamide To a stirred solution of N-{ 2-chloro-5-[(4',6'-O-ethylidene)-p1-D-maltosyloxy methyl]-phenyl}-acetamide (0.323 g, 0.587 mmol) in THF (4.0 mL) at -40 oC was added collidine (4.0 mL, 30.3 mmol) dropwise followed by dropwise addition of BzC1 (0.0818 mL, 0.704 mmol). After 2 h at this temperature, it was warmed to rt 15 and stirred an additional 18 h. At this point, the solvent was distilled off using the high vac, and the residue was diluted with EtOAc (200 mL). This layer was washed with 1N HC1 (20 mL), sat. NaHCO 3 (20 mL), and brine (20 mL) and then dried (MgSO 4 ). After concentration, the oilly residue was purified by flash chromatography (1% to 11% MeOH:CHC1, gradient) and recrystallization (EtOAc:Et20) to afford the 20 product (0.209 g, 54%) as a white glassy solid, mp 166-169 oC; 'H NMR (DMSO-d) 8 1.19 (d, J = 5.1 Hz, 3H), 2.04 (s, 3H), 3.09 (t, J = 9.4 Hz, 1H), 3.14-3.21 (m, 1H), 3.27-3.36 (m, 2H), 3.45-3.52 (m, 2H), 3.52-3.60 (m, 2H), 3.73 (ddd, J = 1.5, 5.1, 9.4 Hz, 1H), 3.89 (dd, J = 4.8, 9.9 Hz, 1H), 4.30 (dd, J = 5.5, 12.1 Hz, 1H), 4.38 (d, J = 7.7 Hz, 1H), 4.53-4.61 (m, 2H), 4.65 (q, J = 5.1, 1H), 4.73 (d, J = 12.5 Hz, 1H), 5.07 25 (d, J = 4.0 Hz, 1H), 5.28 (d, J = 5.3 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.55 (d, J = 2.9 Hz, 1H), 5.77 (d, J = 5.9 Hz, 1H), 7.18 (dd, J = 2.0, 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.50-7.55 (m, 2H), 7.62-7.68 (m, 2H), 7.96-8.00 (m, 2H), 9.50 (s, 1H); IR (KBr) 3450, 3360, 2990, 2910, 2860, 1725, 1750, 1600, 1520, 1450, 1420, 1385, 1375, 1260, 1230, 1130, 1110, 1075, 1055, and 1020 cm'; mass spectrum [(+) FAB], 30 m/z 654/656 (M + H)+, 676/678 (M + Na) , 692/694 (M + K)+; Anal. Calcd. for

C

3 0

H

36 C1N0 13 : C, 55.09; H, 5.55; N, 2.14, Found: C, 54.76; H, 5.40; N, 2.00.

WO 00/31096 PCT/US99/27828 - 35 Example 3 (R)-N-[2-Chloro-5-[[[2.3-di-O-acetyl-6-O-benzoyl-4-O-(2,3-di-O-acetvy1-4,6-O ethylidene-ax-D- lucopvranosvyl)--D-glucopvranosyll] oxylmethyl] phenyll]acetamide To a stirred solution of (R)-N-[5-[[[6-O-benzoyl-4-O-(4,6-O-ethylidene-a-D 5 glucopyranosyl)-p3-D-glucopyranosyl]oxy]methyl]-2-chlorophenyl]acetamide (0.086 g, 0.131 mmol) and triethylamine (0.161 mL, 1.15 mmol) in CH 2 C1 2 (6 mL) at rt was added dropwise acetic anhydride (0.0544 mL, 0.576 mmol) followed by a catalytic amount of DMAP (0.0064 g, 0.0524 mmol). After 18 h, the mixture was diluted with EtOAc (200 mL). This layer was washed with 1 N HC1 (20 mL), sat. aq. NaHCO 3 (20 10 mL), and brine (20 mL) and then dried (Na 2

SO

4 ). After concentration, the residue was purified by preparatory plate chromatography (10:90 MeOH:CHC13) to afford the product (0.071 g, 66%) as a white, mp >87 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 1.13 (d, J = 4.8 Hz, 3H), 1.92 (s, 3H), 1.95 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 2.05 (s, 3H), 3.31-3.39 (m, 1H), 3.55-3.67 (m, 3H), 4.10-4.19 (m, 2H), 4.41 (dd, J = 3.1, 12.3 Hz, 15 1H), 4.54 (d, J = 12.7 Hz, 1H), 4.64-4.74 (m, 3H), 4.77 (dd, J = 8.3, 9.4 Hz, 1H), 4.82 (dd, J = 4.0, 10.1 Hz, 1H), 4.89 (d, J = 7.9 Hz, 1H), 5.18 (t, J = 9.7 Hz, 1H), 5.29 (d, J = 4.2 Hz, 1H), 5.33 (t, J = 9.0 Hz, 1H), 7.04 (dd, J = 1.5, 8.1 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H), 7.61 (s, 1H), 7.68 (t, J = 7.5 Hz, 1H), 8.01-8.07 (m, 2H), 9.45 (s, 1H); IR (KBr) 3410, 2940, 2850, 1755, 1690, 1590, 1530, 20 1440, 1420, 1370, 1240, 1135, 1060, and 1030 cm'; mass spectrum [(+) FAB], m/z 822/824 (M + H)', 844/846 (M + Na)'; Anal. Calcd. for C 3 8

H

44 C1N0 1 7 1.5 H20: C, 53.74; H, 5.58; N, 1.65, Found: C, 53.69; H, 5.14; N, 1.57. Example 4 25 N- {2-Chloro-5-[(4',6'-O-propylidene- -D-maltosyl)-oxy-methyll]-phenylI }-acetamide The title compound was prepared as a white solid (0.309 g, 57%) from N-[2 chloro-5-(f-D-maltosyl-oxymethyl)-phenyl]-acetamide using propionaldehyde diethyl acetal and a procedure similar to step 5 of Example 1, mp >64 oC (decomp.); 'H NMR (DMSO-d) 6 0.86 (t, J = 7.5 Hz, 3H), 1.48-1.58 (m, 2H), 2.07 (s, 3H), 3.04 30 3.14 (m, 2H), 3.25-3.58 (m, 8H), 3.68 (dd, J = 6.2, 10.5 Hz, 1H), 3.95 (dd, J = 4.6, 9.9 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.48 (t, J = 5.1 Hz, 1H), 4.65 (t, J = 5.9 Hz, 1H), 4.67 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.08 (d, J = 4.0 Hz, 1H), 5.20 (d, J = 5.3 WO 00/31096 PCT/US99/27828 - 36 Hz, 1H), 5.24 (d, J = 5.3 Hz, 1H), 5.48 (d, J = 3.3 Hz, 1H), 5.57 (d, J = 6.6 Hz, 1H1), 7.22 (dd, J = 1.8, 8.3 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3400, 2980, 2920, 2840, 1675, 1580, 1530, 1460, 1425, 1375, 1310, 1275, 1150, 1060, and 1020 cm"; mass spectrum [(+) FAB], m/z 586/588 (M + Na) ; Anal. 5 Calcd. for C 2 4

H

34 C1N0 1 2 * 1.0 H20: C, 49.53; H, 6.23; N, 2.41, Found: C, 49.89; H, 6.38; N, 2.19. Example 5 N-f 5-f[(6-O-Benzovl-4',6'-O-propylidene--D-maltosyl)-oxv-methvll-2-chloro 10 phenvyl }-acetamide The title compound was prepared as a white solid (0.140 g, 47%) from N-{2 chloro-5-[(4',6'-O-propylidene-p-D-maltosyl)-oxy-methyl]-phenyl }-acetamide using a procedure similar to Example 2, mp >88 oC (decomp.); 1H NMR (DMSO-d) 6 0.84 (t, J = 7.5 Hz, 3H), 1.45-1.57 (m, 2H), 2.04 (s, 3H), 3.08 (t, J = 5.1 Hz, 1H), 3.17 (dd, 15 J = 8.3, 13.2 Hz, 1H), 3.26-3.37 (m, 2H), 3.45-3.59 (m, 4H11), 3.70-3.77 (m, 1H), 3.91 (dd, J = 4.6, 9.7 Hz, 1H), 4.30 (dd, J = 5.3, 12.1 Hz, 1H), 4.38 (d, J = 7.7 Hz, 1H), 4.43 (t, J = 4.8 Hz, 1H1), 4.53-4.61 (m, 2H), 4.73 (d, J = 12.3 Hz, 1H), 5.07 (d, J = 3.5 Hz, 1H), 5.25 (d, J = 5.3 Hz, 1H), 5.34 (d, J = 5.1 Hz, 1H), 5.56 (d, J = 2.2 Hz, 1H11), 5.77 (d, J = 5.9 Hz, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.53 (t, J 20 = 7.7 Hz, 2H1), 7.61-7.68 (m, 2H), 7.98 (d, J = 7.5 Hz, 2H), 9.45 (s, 1H); IR (KBr) 3410, 2970, 2920, 2860, 1720, 1675, 1590, 1530, 1450, 1420, 1375, 1270, 1060, 1020, and 720 cm-'; mass spectrum [(-) FAB], m/z 666 (M - H); Anal. Calcd. for

C

31

H

38 C1NO 1 3 : C, 55.73; H, 5.73; N, 2.09, Found: C, 55.67; H, 5.71; N, 2.09. 25 Example 6 N-(5- { [4'.6'-O-Benzvlidene-6-O-(4-toluenesulfonv1)-B-D-maltosyll-oxy-methyl 1-2 chloro-phenvl)-acetamide step 1 N-{5-[(4',6'-O-Benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl} 30 acetamide To a stirred solution of N-[2-chloro-5-(p-D-maltosyl-oxymethyl)-phenyl] acetamide (14.15 g, 27.0 mmol) in DMF (325 mL) at rt was added benzaldehyde WO 00/31096 PCT/US99/27828 - 37 dimethyl acetal (8.11 mL, 54.0 mmol) dropwise followed by TsOH.H 2 0 (2.57 g, 13.5 mmol). The reaction mixture was heated to 60 oC for 6 h and then quenched with

K

2

CO,

3 (1.87 g, 13.5 mmol) with an additional 0.5 h heating at this temperature. At this point, the solution was filtered hot, and the solvent was distilled off using the 5 high vac. The residue was purified by flash chromatography (80:2:1 to 20:2:1 EtOAc:EtOH:H 2 0O gradient) to afford the product (10.8 g, 65%) as a white solid, mp 143-147 oC; 'H NMR (DMSO-d 6 ) 8 2.08 (s, 3H), 3.07-3.12 (m, 1H), 3.28-3.50 (m, 5H), 3.51-3.60 (m, 2H), 3.64-3.75 (m, 3H), 4.10-4.12 (m, 1H), 4.30 (d, J = 7.9 Hz, 1H), 4.67 (t, 5.9 Hz, 1H), 4.68 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = 4.0 Hz, 10 1H), 5.25 (d, J = 5.1 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 5.51 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.63 ( d, J = 6.8 Hz, 1H), 7.22 (dd, J = 1.5, 8.3 Hz, 1H), 7.35-7.38 (m, 3H), 7.42-7.46 (m, 3H), 7.66 (s, 1H), 9.53 (s, 1H); IR (KBr) 3500, 3410, 2910, 2850, 1700, 1600, 1550, 1440, 1425, 1375, 1310, 1230, 1150, 1070, and 1030 cm'; mass spectrum [(+) FAB], m/z 634 (M + Na)*; Anal. Calcd. for C 28

,H

34 CINO 1 2 1.0 HO: 15 C, 53.38; H, 5.76; N, 2.22, Found: C, 53.58; H, 5.62; N, 2.25. step 2 N-(5-{[4',6'-O-Benzylidene-6-O-(4-toluenesulfonyl)-p-D-maltosyl].-oxy-methyl}-.2.

chloro-phenyl)-acetamide 20 At 0 oC, to a stirred solution of N-{5-[(4',6'-O-benzylidene-p-D maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide (1.81 g, 2.96 mmol) in pyridine (6.0 mL) was added a solution of p-toluenesulfonyl chloride (0.686 g, 3.60 mmol) in CH,C1 2 (3.75 mL). After 2 h, additional p-toluenesulfonyl chloride (0.686 g, 3.60 mmol) in CH 2 C1 2 (3.75 mL) was added and the solution was stirred at 0 oC for 2h. 25 The reaction was quenched with ice cold H 2 0 (50 mL) and extracted with EtOAc. The combined organic extracts were washed successively with sat. aq. NaHCO, (2x), sat. aq. CuSO, (2x), brine (2x), dried (Na 2 SO4) and concentrated. Purification by flash chromatography (5-10% MeOH:CH 2 C 2 gradient) gave 0.930 g, (41%) of a colorless solid, mp 105-120 oC; 'H NMR (DMSO-d) 8 2.08 (s, 3H), 2.33 (s, 3H), 3.04-3.09 30 (m, 1H), 3.27-3.45 (m, 4H), 3.49-3.53 (m, 1H), 3.60-3.65 (m, 3H), 3.95 (d, 1H), 4.13 (dd, 1H), 4.29-4.33 (m, 2H), 4.46 (d, 1 H), 4.62 (d, 1 H), 5.05 (d, 1H), 5.33-5.35 (m, 2H), 5.55 (d, 1H), 5.57 (s, 1H), 5.75 (d, 1H), 7.18 (d, 1H), 7.35-7.47 (m, 8H), 7.78 WO 00/31096 PCT/US99/27828 - 38 (d, 2H), 9.53 (s, 1H); mass spectrum [(+) ESI], m/z 766/768 (M + H)+, 783/785 (M +

NH

4 )+; Anal. Calcd. for C 3 5 H4 0 NC10, 4 S H20: C, 53.60; H, 5.40; N, 1.79, Found: C, 53.46; H, 5.18; N, 1.80. 5 Example 7 N-(5- { [2.3.2'.3'-Tetra-O-acetyl-4' ,6'-O-benzylidene-6-O-(4-toluenesulfonvl)-3-D maltosyll-oxy-methyl }-2-chloro-phenvyl)-acetamide The title compound was prepared as a colorless solid (0.942 g, 99%) from N (5-{ [4',6'-O-benzylidene-6-O-(4-toluenesulfonyl)--D-maltosyl]-oxy-methyl }-2 10 chloro-phenyl)-acetamide using a procedure similar to Example 3, mp 116-122 oC; 'H NMR (DMSO-d) a 1.91 (s, 3H), 1.92 (s, 3H), 1.96 (s, 3H), 2.00 (s, 3H), 2.08 (s, 3H), 2.29 (s, 3H), 3.68 (dd, 1H), 3.77 (t, 1H), 3.85 (t, 1H), 3.90 (t, 1H), 3.97-4.00 (m, 1H), 4.21 (dd, 1H), 4.32 (s, 2H), 4.39 (d, 1H), 4.56 (d, 1H), 4.60 (d, 1H), 4.78 (d, 1H), 4.86 (dd, 1H), 5.17-5.30 (m, 3H), 5.65 (s, 1H), 7.03 (d, 1H), 7.34-7.41 (m, 7H), 15 7.46 (d, 1H), 7.59 (s, 1H), 7.80 (d, 2H), 9.52 (s, 1H); mass spectrum [(+) ESI], m/z 934/936 (M + H)+; Anal. Calcd. for C 43

H

4 8 NC10 8 S: C, 55.27; H, 5.17; N, 1.50, Found: C, 55.07; H, 5.05; N, 1.47. Example 8 20 N-f 5-[(6-O-Benzvl-4',6'-O-benzylidene-I-D-maltosyl)-oxy-methyll-2-chloro phenvl } -acetamide step 1 N-{5-[(2,2',3,3'-Tetra-O-acetyl-4',6' -O-benzylidene-o-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-acetamide 25 A solution containing N-(5- { [2,3,2',3'-tetra-O-acetyl-4',6'-O-benzylidene-6 O-(4-toluenesulfonyl)-p-D-maltosyl]-oxy-methyl

}-

2 -chloro-phenyl)-acetamide (1.021 g, 1.093 mmol) and sodium formate (0.1858 g, 2.732 mmol) in EtOH:DMSO:H 2 0 (2:2:1, 21.9 mL) was heated at 100oC for 2 days. The reaction was cooled to ambient temperature, diluted with 10% CH 2 C1 2 :EtOAc (100 mL), washed with brine (3x), 30 dried (MgSO 4 ) and concentrated in vacuo. Purification by flash chromatography (1,2 and 3% MeOH:CHC1 3 gradient) gave 0.446 g (52%) of title compound as a colorless solid; 'H NMR (DMSO-d 6 ) 8 1.93 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 2.01 (s, 3H), WO 00/31096 PCT/US99/27828 - 39 2.08 (s, 3H), 3.68-3.99 (m, 7H), 4.19-4.22 (m, 1H), 4.57 (d, J = 12.7 Hz, 1H), 4.64 4.87 (m, 4H), 5.00 (br.s, 1H), 5.21-5.33 (m, 3H), 5.63 (s, 1H), 7.08 (dd, J = 8.3, 1.8 Hz, 1H), 7.38 (s, 5H), 7.47 (d, J = 8.2 Hz, 1H), 7.64 (s, 1H), 9.53 (s, 1H). 5 step 2 N-{5-[(2,2',3,3'-Tetra-O-acetyl-6-O-benzyl-4',6'-O-benzylidene-p-D-maltosyl) oxy-methyl]-2-chloro-phenyl}-acetamide At ambient temperature, to a stirred solution containing N-{5-[(2,2',3,3'-tetra O-acetyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl} 10 acetamide (0.221 g, 0.283 mmol) and benzyl 2 ,2,2-trichloroacetimidate (0.105 mL, 0.567 mmol) in 10% CH 2 C1 2 :benzene (10 mL) was added trifluoromethane sulfonic acid (1 drop). After 16 h, the reaction was diluted with 5% MeOH:CHC1 3 (10 mL), filtered through a 1" silica gel pad eluting with 5% MeOH:CHC13 and concentrated in vacuo. Purification by flash chromatography (1 and 2% MeOH:CHC13 gradient) gave 15 0.134 g (54%) of title compound as a colorless solid; 'H NMR (DMSO-d 6 ) 6 1.94 (s, 3H), 1.96 (s, 3H), 1.98 (s, 3H), 2.01 (s, 3H), 2.07 (s, 3H), 3.69-4.07 (m, 8H), 4.54 4.59 (m, 3H), 4.69-4.77 (m, 2H), 4.82-4.86 (m, 2H), 5.23-5.34 (m, 3H), 5.61 (s, 1H), 7.09 (dd, J = 8.3, 1.7 Hz, 1H), 7.27-7.37 (m, 10H), 7.46 (d, J = 8.2 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H). 20 step 3 N-{5-[(6-O-Benzyl-4',6'-O-benzylidene-p1-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-acetamide The title compound was prepared as a colorless solid (0.085 g, 65%) from N 25 {5-[(2,2',3,3'-tetra-O-acetyl-6-O-benzyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl }-acetamide using a procedure similar to step 4 of Example 1, mp 98-105 oC; 'H NMR (DMSO-d) 8 2.06 (s, 3H), 3.09-3.11 (m, 1H), 3.28-3.75 (m, 10H), 3.99 (dd, 1H), 4.33 (d, J = 7.7 Hz, 1H), 4.50 (s, 1H), 4.51 (s, 1H), 4.66 (ABq, J = 12.6 Hz, A6 = 0.08, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.30 (d, J = 9.0 Hz, 1H), 30 5.31 (d, J = 9.0 Hz, 1H), 5.56-5.57 (m, 2H), 5.70 (d, J = 6.6 Hz, 1H), 7.21-7.38 (m, 9H), 7.42 - 7.45 (m, 3H), 7.66 (s, 1H), 9.52 (s, 1H); mass spectrum [(+) FAB], m/z WO 00/31096 PCT/US99/27828 - 40 724 (M + H)+; Anal. Calcd. for C 3 5

H

40 NC10 2 0.5 HO: C, 59.11; H, 5.81; N, 1.97, Found: C, 59.12; H, 5.76; N, 1.98. Example 9 5 N-f 5-[(6-O-Benzvl-4',6' -O-ethylidene-B-D-maltosvl)-oxy-methyll-2-chloro-phenyl

I}

acetamide step 1 N-{5-[(2,2',3,3'-Tetra-O-acetyl-6-O-benzyl-P-D-maltosyl)-oxy-methyl]-2-chioro phenyl}-acetamide 10 At ambient temperature, to a stirred solution of N-{5-[(2,2',3,3'-tetra-O-acetyl -6-O-benzoyl-4',6'-O-benzylidene--D-maltosyl)-oxy-methyl]-2-chloro-phenyl

}

acetamide (0.202 g, 0.232 mmol) in MeOH (5 mL) was added IM ethereal HC1. After 2 h, the reaction was quenched with sat. aq. NaHCO 3 (25 mL), diluted with H 2 0 (25 mL), extracted with EtOAc, dried (Na 2

SO

4 ) and concentrated. Purification by 15 flash chromatography (5% MeOH:CHC13) gave 0.136 g (75%) of title compound; 'H NMR (DMSO-d) a 1.92 (s, 3H), 1.95 (s, 6H), 2.00 (s, 3H), 2.07 (s, 3H), 3.49-3.56 (m, 4H), 3.75-3.94 (m, 4H), 4.50-4.59 (m, 5H), 4.67-4.76 (m, 2H), 4.83 (d, J = 7.9 Hz, 1H), 5.06-5.13 (m, 1H), 5.21-5.29 (m, 2H), 5.44 (d, J = 6.0 Hz, 1H), 7.08 (dd, J = 8.1, 1.5 Hz, 1H), 7.26-7.36 (m, 5H), 7.45 (d, J = 8.2 Hz, 1H), 7.64 (s, 1H), 9.52 (s, 20 1H). step 2 N-{5-[(2,2',3,3'-Tetra-O-acetyl-6-0-benzyl-4',6'-O-ethylidene-o-D-maltosyl)-oxy methyl]-2-chloro-phenyl}-acetamide 25 A stirred solution containing N- { 5-[(2,2',3,3'-tetra-O-acetyl-6-O-benzyl-0-D maltosyl)-oxy-methyl]-2-chloro-phenyl}-acetamide (0.274 g, 0.350 mmol), priopionaldehyde (45.5 [tL, 0.630 mmol) and camphor sulfonic acid (18.3 mg, 0.0787 mmol) in benzene (6.3 mL) was refluxed with Dean-Stark azeotropic removal of water. After 2.5 h, The reaction was cooled to room temperature, quenched with 30 NaHCO 3 (25 mL), extracted with EtOAc and dried (Na 2 SO4). Purification by flash chromatography (1, 2 and 3% MeOH:CHC1 3 gradient) gave 0.346 g (96%) of title compound; 'H NMR (DMSO-d) 6 0.82 (t, 3H), 1.48-1.53 (m, 2H), 1.92 (s, 3H), 1.95 WO 00/31096 PCT/US99/27828 -41 (s, 3H), 1.97 (s, 3H), 2.01 (s, 3H), 2.07 (s, 3H), 3.41-3.48 (m, 1H), 3.60-3.64 (m, 2H), 3.71-4.03 (m, 5H), 4.49-4.69 (m, 4H), 4.70-4.85 (m, 4H), 5.14-5.32 (m, 3H), 7.07-7.36 (m, 6H), 7.46 (d, J = 8.2 Hz, 1H), 7.64 (s, 1H), 9.52 (s, 1H). 5 step 3 N-{5-[(6-O-Benzyl-4',6'-O-ethylidene-p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-acetamide A solution containing N- {5-[(2,2',3,3'-tetra-O-acetyl-6-O-benzyl-4',6'-O ethylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl}-acetamide (0.217 g, 0.264 10 mmol) and 25 weight% NaOMe in MeOH (0.0285 g, 0.132 mmol) in MeOH (5.3 mL) was refluxed for 3h. The reaction was cooled to room temperature and concentrated. Purification by flash chromatography (10% MeOH/CH 2 C1 2 gradient) gave the product (0.100g, 58%) as a white solid, mp 182-185 oC; 'H NMR (DMSO d6) 8 0.85 (t, J = 7.5 Hz, 3H), 1.21-1.55 (m, 2H), 2.05 (s, 3H), 3.05-3.13 (m, 2H), 15 3.24-3.70 (m, 9H), 3.83 (dd, J = 9.8, 4.7 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.43-4.49 (m, 3H), 4.63 (ABq, J = 12.4 Hz, A6 = 0.07, 2H), 5.07 (d, J = 3.5 Hz, 1H), 5.24 (d, J = 5.3 Hz, 1H), 5.31 (d, J = 5.3 Hz, 1H), 5.55 (d, J = 2.6 Hz, 1H), 5.65 (d, J = 6.6 Hz, 1H), 7.17-7.34 (m, 6H), 7.41 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 9.55 (s, 1H). mass spectrum [(+) ESI] 671 (M + NH 4 )*; Anal. Calcd. for C, 31

H

40 NC10 1 2 : C, 56.92; H, 20 6.16; N, 2.14, Found: C, 56.69; H, 6.33; N, 1.99. Example 10 N-(2-Chloro-5- [ 4'.6'-O-(4-nitro)-benzvlidene--D-maltosvl1-oxy-methyl }-phenvyl) acetamide 25 To a stirred solution of N-[ 2 -chloro-5-(-D-maltosyl-oxymethyl)-phenyl] acetamide (0.500 g, 0.954 mmol) in DMF (30 mL) at rt was added 3-nitro benzaldehyde dimethyl acetal (0.752 g, 3.82 mmol) followed by CSA (0.111 g, 0.477 mmol). The reaction mixture was heated to 60 oC for 18 h and was about 35% complete by TLC. Another 0.5 eq. CSA (0.11 g) added and heated at 90 oC for 3 h. 30 The reaction was then quenched with K2CO3 (0.132 g, 0.954 mmol) with an additional 0.5 h heating at 60 oC. At this point, the solution was filtered hot, and the solvent was distilled off using the high vac. The residue was purified by flash WO 00/31096 PCT/US99/27828 - 42 chromatography (40:2:1 to 20:2:1 EtOAc:EtOH:H 2 0 gradient) to afford the product (0.262 g, 42%) as a white solid, mp 221-223 oC; 'H NMR (DMSO-d) a 2.07 (s, 3H), 3.06-3.12 (m, 1H), 3.26-3.49 (m, 5H), 3.49-3.62 (m, 2H), 3.68-3.77 (m, 3H), 4.11 4.20 (m, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.67 (t, J = 5.7 Hz, 1H), 4.68 (ABq, J = 12.3 5 Hz, A6 = 0.22, 2H), 5.16 (d, J = 3.7 Hz, 1H), 5.25 (d, J = 4.8 Hz, 1H), 5.36 (d, J = 4.8 Hz, 1H), 5.49 (d, J = 3.1 Hz, 1H), 5.62 (d, J = 6.6 Hz, 1H), 5.74 (s, 1H), 7.22 (dd, J = 1.8, 8.1 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 7.73 (d, J = 8.8 Hz, 2H), 8.25 (dt, J = 2.2, 9.0 Hz, 2H), 9.52 (s, 1H); IR (KBr) 3410, 2910, 2870, 1670, 1610, 1590, 1530, 1440, 1420, 1355, 1320, 1265, 1140, 1075, and 1035 cm'; mass spectrum [(-) 10 FAB], m/z 655 (M - H); Anal. Calcd. for C 2 8

H

3 3 C1N 2 0, 4 : C, 51.19; H, 5.06; N, 4.26, Found: C, 50.87; H, 4.87; N, 4.32. Example 11 N-(5- { [6- O-Benzovl-4',6'-O-(4-nitro)-benzvlidene- -D-maltosyll-oxy-methyl }-2 15 chloro-phenvyl)-acetamide The title compound was prepared as a white solid (0.080 g, 35%) from N-(2 chloro-5- { [4',6'-O-(4-nitro)-benzylidene-0-D-maltosyl]-oxy-methyl } -phenyl) acetamide using the procedure of Example 2, mp >167 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 2.04 (s, 3H), 3.15-3.22 (m, 1H), 3.37-3.43 (m, 2H), 3.51 (td, J = 2.9, 20 8.8 Hz, 1H), 3.57-3.64 (m, 3H), 3.70-3.78 (m, 2H), 4.09 (dd, J = 4.6, 9.9 Hz, 1H), 4.35 (dd, J = 5.1, 12.3 Hz, 1H), 4.39 (d, J = 7.7 Hz, 1H), 4.57-4.63 (m, 1H), 4.65 (ABq, J = 12.3 Hz, AS = 0.14, 2H), 5.15 (d, J = 4.0 Hz, 1H), 5.36 (d, J = 5.3 Hz, 1H), 5.41 (d, J = 5.3 Hz, 1H), 5.57 (d, J = 3.1 Hz, 1H), 5.70 (s, 1H), 5.81 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 1.8, 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.50-7.56 (m, 2H), 7.62 25 7.72 (m, 4H), 7.97-8.01 (m, 2H), 8.24 (dt, J = 2.4, 9.2 Hz, 2H), 9.45 (s, 1H); IR (KBr) 3410, 2850, 1725, 1660, 1610, 1590, 1530, 1445, 1420, 1355, 1270, 1120, 1075, 1025, and 715 cm'; mass spectrum [(+) FAB], m/z 783 (M + Na)'; Anal. Calcd. for C 3 5

H

3 7 C1N 2 0 1 5 O, - 1.0 -LO: C, 53.95; H, 5.05; N, 3.60, Found: C, 53.86; H, 4.75; N, 3.51. 30 WO 00/31096 PCT/US99/27828 - 43 Example 12 N- {2-Chloro-5-[(4'.6'-O-(4-chloro)-benzvlidene- -D-maltosyl)-oxv-methyll phenyl I -acetamide The title compound was prepared as a white glass (0.315 g, 51%) from N-[2 5 chloro-5-(p-D-maltosyl-oxymethyl)-phenyl]-acetamide using p-chloro-benzaldehyde dimethyl acetal and the procedure of Example 10, mp >97 oC (decomp.); 1 H NMR (DMSO-d 6 ) a 2.07 (s, 3H), 3.09 (t, J = 8.8 Hz, 1H), 3.28-3.48 (m, 5H), 3.49-3.61 (m, 2H), 3.61-3.75 (m, 3H), 4.11 (d, J = 5.3 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.63-4.72 (bs, 1H), 4.68 (ABq, J = 12.3 Hz, A6 = 0.22, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.21-5.36 10 (bs, 2H), 5.47-5.53 (bs, 1H), 5.57-5.66 (bs, 1H), 5.59 (s, 1H), 7.22 (dd, J = 2.0, 8.3 Hz, 1H), 7.42-7.48 (m, 5H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3390, 2920, 2850, 1670, 1590, 1530, 1500, 1450, 1420, 1365, 1300, 1140, 1070, 1030, and 815 cm-'; mass spectrum [(+) FAB], m/z 668 (M + Na)*; Anal. Calcd. for C 28

H

33 C1 2

NO

1 2 . 0.5 1-20: C, 51.31; H, 5.23; N, 2.14, Found: C, 51.13; H, 5.44; N, 1.92. 15 Example 13 N- { 5-[(6-O-Benzovl-4'.6'-O-(4-chloro)-benzvlidene- -D-maltosyl)-oxv-methyll-2 chloro-phenvl } -acetamide The title compound was prepared as a white solid (0.158 g, 50%) from N-{2 20 chloro-5-[(4',6'-O-(4-chloro)-benzylidene-p-D-maltosyl)-oxy-methyl]-phenyl

}

acetamide using a procedure similar to Example 2, mp >182 oC (decomp.); 1 H NMR (DMSO-d) 8 2.05 (s, 3H), 3.15-3.22 (m, 1H), 3.28-3.43 (m, 2H), 3.48-3.63 (m, 4H), 3.67-3.73 (m, 1H), 3.73-3.78 (m, 1H1), 4.03-4.07 (m, 1H1), 4.32-4.37 (m, 1H), 4.39 (d, J = 7.9 Hz, 1H), 4.57-4.63 (m, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 5.14 (d, 25 J = 4.0 Hz, 1H), 5.36 (dd, J = 2.6, 5.1 Hz, 2H1), 5.54 (s, 1H), 5.56 (d, J = 3.1 Hz, 1H), 5.79 (d, J = 6.4 Hz, 1H), 7.19 (dd, J = 2.0, 8.3 Hz, 1H), 7.40 (d, J = 8.3 Hz, 1H), 7.43 (s, 4H), 7.53 (t, J = 7.9 Hz, 2H), 7.63-7.68 (m, 2H), 7.99 (dd, J = 0.9, 7.9 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3450, 3380, 2960, 2900, 2860, 1730, 1700, 1665, 1590, 1530, 1495, 1440, 1415, 1365, 1310, 1280, 1140, 1075, 1050, 1035, 1015, 820, and 720 cm 30 ; mass spectrum [(+) FAB], m/z 750 (M + H)', 772 (M + Na)*; Anal. Calcd. for

C

3 5

H

3 7 C1 2 N0 13 : C, 56.01; H, 4.97; N, 1.87, Found: C, 55.67; H, 4.91; N, 1.87.

WO 00/31096 PCT/US99/27828 - 44 Example 14 N- 2-Chloro-5-[(4',6'-O-isobutylidene- -D-maltosvl)-oxy-methyll-phenvyl acetamide The title compound was prepared as a white solid (0.250 g, 45%) from N-[2 5 chloro-5-(P3-D-maltosyl-oxymethyl)-phenyl]-acetamide using isobutyraldehyde diethyl acetal and the procedure of Example 10, mp >122 oC (decomp.); 'H NMR (DMSO-d) 8 0.87 (dd, J = 5.5, 6.6 Hz, 6H), 1.68-1.78 (m, 1H), 2.07 (s, 3H), 3.04 3.13 (m, 2H), 3.24-3.55 (m, 8H), 3.68 (dd, J = 6.2, 10.5 Hz, 1H), 3.97 (dd, J = 4.6, 9.7 Hz, 1H), 4.27 (s, 1H), 4.28 (d, J = 3.7 Hz, 1H), 4.65 (t, J = 5.9 Hz, 1H), 4.67 10 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.06 (d, J = 4.0 Hz, 1H), 5.17 (d, J = 5.3 Hz, 1H), 5.24 (d, J = 5.3 Hz, 1H), 5.50 (d, J = 3.3 Hz, 1H), 5.59 (d, J = 6.6 Hz, 1H), 7.22 (dd, J = 1.5, 7.9 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3420, 2960, 2910, 2830, 1670, 1590, 1530, 1460, 1420, 1370, 1310, 1255, 1145, 1080, 1055, and 1030 cm'; mass spectrum [(-) ESI], m/z 576 (M - H); Anal. Calcd. 15 for C 25

H

3 6 C1NO 2 * 0.5 H 2 0: C, 51.15; H, 6.35; N, 2.39, Found: C, 51.06; H, 6.56; N, 2.45. Example 15 N- { 5-f(6-O-Benzov1-4'.6'-O-isobutvlidene- -D-maltosv1l)-oxy-methyll-2-chloro 20 phenvl}-acetamide The title compound was prepared as a white solid (0.079 g, 41%) from N-{2 chloro-5-[(4',6'-O-isobutylidene-p-D-maltosyl)-oxy-methyl]-phenyl }-acetamide using the procedure of Example 2, mp >123 oC (decomp.); 'H NMR (DMSO-d) 6 0.85 (t, J = 6.4 Hz, 6H), 1.66-1.75 (m, 1H), 2.05 (s, 3H), 3.07 (t, J = 9.4 Hz, 1H), 25 3.15-3.21 (m, 1H), 3.26-3.36 (m, 2H), 3.46-3.60 (m, 4H), 3.72-3.77 (m, 1H), 3.92 (dd, J = 4.8, 10.1 Hz, 1H), 4.23 (d, J = 4.8 Hz, 1H), 4.30 (dd, J = 5.1, 12.1 Hz, 1H), 4.38 (d, J = 7.7 Hz, 1H), 4.57 (d, J = 10.5 Hz, 1H), 4.64 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 5.06 (d, J = 4.0 Hz, 1H), 5.21 (d, J = 4.8 Hz, 1H), 5.34 (d, J = 5.1 Hz, 1H), 5.57 (d, J = 2.2 Hz, 1H), 5.76 (d, J = 5.9 Hz, 1H), 7.18 (dd, J = 1.5, 8.3 Hz, 1H), 7.40 30 (d, J = 8.3 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.61-7.68 (m, 2H), 7.96-8.01 (m, 2H), 9.50 (s, 1H): IR (KBr) 3410, 2960, 2910, 2840, 1725, 1660, 1610, 1590, 1530, 1440, 1425, 1375, 1270, 1080, 1055, 1025, and 715 cm'; mass spectrum [(-) APCI], m/z WO 00/31096 PCT/US99/27828 -45 681.0/683.1 (M), Anal. Calcd. for C 32

H

40 C1NO, - 3 . 1.0 H 2 0: C, 54.90; H, 6.05; N, 2.00, Found: C, 54.95; H, 5.90; N, 1.94. Example 16 5 N- { 5-[(4',6'-O-(( 1R)-2-Phenyl-ethylidene)- -D-maltosyloxy)-methyll-2-chloro phenyl -acetamide The title compound was prepared as a white solid (0.210 g, 35%) from N-[2 chloro-5-(P-D-maltosyl-oxymethyl)-phenyl]-acetamide using phenylacetaldehyde dimethyl acetal and the procedure of Example 10, mp >106 oC (decomp.); 'H NMR 10 (DMSO-d 6 ) 8 2.07 (s, 3H), 2.81 (dd, J = 6.4, 14.1, 1H), 2.91 (dd, J = 4.0, 14.1 Hz, 1H), 3.04-3.11 (m, 1H), 3.16 (t, J = 9.4 Hz, 1H), 3.26-3.54 (m, 7H), 3.58 (td, J = 5.1, 10.1 Hz, 1H), 3.65-3.72 (m, 1H), 3.93 (dd, J = 4.8, 9.9 Hz, 1H), 4.29 (d, J = 7.7 Hz, 1H), 4.65 (t, J = 5.9 Hz, 1H), 4.67 (ABq, J = 12.3 Hz, A6 = 0.22, 2H), 4.75 (dd, J = 4.2, 6.2 Hz, 1H), 5.09 (d, J = 3.7 Hz, 1H), 5.23 (dd, J = 5.3, 10.1 Hz, 2H), 5.47 (d, J 15 = 3.5 Hz, 1H), 5.57 (d, J = 6.6 Hz, 1H), 7.17-7.30 (m, 6H), 7.44 (d, J = 8.1 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3400, 2920, 2850, 1670, 1590, 1530, 1450, 1420, 1375, 1310, 1250, 1150, 1130, 1060, 1025, and 750 cm'; mass spectrum [(+) FAB], m/z 648 (M + Na)*; Anal. Calcd. for C 2 9H 3 6 C1NO 1 2 2.75 HO 2 0: C, 51.56; H, 6.19; N, 2.07, Found: C, 51.47; H, 5.52; N, 2.13. 20 Example 17 N- { 5-[(6- O-Benzoyl-4',6'- O-((1R)-2-phenvl-ethvlidene)- -D-maltosvloxy)-methyll 2-chloro-phenv1 I -acetamide The title compound was prepared as a white solid (1.25 g, 63%) from N-{5 25 [(4',6'-O-((1R)-2-phenyl-ethylidene)-p-D-maltosyloxy)-methyl]-2-chloro-phenyl

}

acetamide using the procedure of Example 2, mp 153-156oC; 'H NMR (DMSO-d) 6 2.05 (s, 3H), 2.78 (dd, J = 6.2, 14.1 Hz, 1H), 2.89 (dd, J = 4.2, 14.3 Hz, 1H), 3.10 3.21 (m, 2H), 3.26-3.37 (m, 2H), 3.47-3.64 (m, 4H), 3.71-3.77 (m, 1H), 3.89 (dd, J = 4.8, 9.9 Hz, 1H), 4.31 (dd, J = 5.3, 12.1 Hz, 1H), 4.38 (d, J = 7.7 Hz, 1H), 4.53-4.60 30 (m, 2H), 4.68-4.77 (m, 2H), 5.07 (d, J = 4.0 Hz, 1H), 5.27 (d, J = 5.5 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.55 (d, J = 2.9 Hz, 1H), 5.77 (d, J = 6.2 Hz, 1H), 7.16-7.28 (m, 6H), 7.40 (d, J = 8.1 Hz, 1H), 7.52 (t, J = 7.7 Hz, 2H), 7.62-7.67 (m, 2H), 7.98 (dd, J WO 00/31096 PCT/US99/27828 - 46 = 0.7, 7.9 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3480, 3370, 2910, 1725, 1695, 1590, 1525, 1450, 1425, 1380, 1355, 1310, 1275, 1250, 1235, 1140, 1120, 1075, 1050, 1035, and 715 cm'; mass spectrum [(-) FAB], m/z 728 (M - H); Anal. Calcd. for C 36

H

40 C1NO 13 : C, 59.22; H, 5.52; N, 1.92, Found: C, 58.93; H, 5.45; N, 1.86. 5 Example 18 N-f{ 2-Chloro-5-[(4'.6'-O-((1R)-3-cvano-propy1idene)-B-D-maltosyloxy)-methyl] phenvyi } -acetamide The title compound was prepared as a tan solid (0.101 g, 18%) from N-[2 10 chloro-5-(P-D-maltosyl-oxymethyl)-phenyl]-acetamide using 3-cyanopropionalde hyde dimethyl acetal and the procedure of Example 10, mp 185-188 oC; 'H NMR (DMSO-d) 5 1.82-1.89 (m, 2H), 2.07 (s, 3H), 2.47-2.55 (m, 2H), 3.04-3.11 (m, 1H), 3.15 (t, J = 9.2 Hz, 1H), 3.24-3.59 (m, 8H), 3.65-3.71 (m, 1H), 3.99 (dd, J = 4.6, 9.9 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.62-4.67 (m, 2H), 4.67 (ABq, J = 12.5 Hz, A6 = 15 0.22, 2H), 5.10 (d, J = 3.7 Hz, 1H), 5.24 (dd, J = 5.3, 7.2 Hz, 2H), 5.48 (d, J = 3.3 Hz, 1H), 5.58 (d, J = 6.6 Hz, 1H), 7.22 (d, J = 1.8, 8.1 Hz, 1H), 7.44 (8.1 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H); IR (KBr) 3540, 3410, 3120, 2930, 2850, 2230, 1685, 1590, 1540, 1450, 1425, 1420, 1370, 1320, 1255, 1150, 1130, 1100, 1065, 1050, 1020, 995, and 890 cm'; mass spectrum [(+) FAB], m/z 611 (M + Na)'; Anal. Calcd. for 20 C H 3 3 C1N 2 01 2 -0.5 I-HLO: C, 50.21; H, 5.73; N, 4.68, Found: C, 50.32; H, 5.51; N, 4.84. Example 19 N- { 5- { [6-O-Benzoyl-4',6'-O-((1R)-3-cvanopropylidene)-B-D-maltos1yloxv]-methyl

}

25 2-chloro-phenvyl -acetamide The title compound was prepared as a white solid (0.038 g, 46%) from N-{2 chloro-5-[(4',6'-O-((1R)-3-cyano-propylidene)-p-D-maltosyloxy)-methyl]-phenyl

}

acetamide using the procedure of Example 2, mp 164-166 oC; 'H NMR (DMSO-d) a 1.79-1.86 (m, 2H), 2.04 (s, 3H), 2.48-2.52 (m, 2H), 3.13 (t, J = 9.2 Hz, 1H), 3.14 30 3.20 (m, 1H), 3.27-3.40 (m, 2H), 3.46-3.60 (m, 4H), 3.71-3.77 (m, 1H), 3.93 (dd, J = 4.6, 9.9 Hz, 1H), 4.30 (dd, J = 5.3, 12.1 Hz, 1H), 4.38 (d, J = 7.9 Hz, 1H), 4.55-4.62 (m, 2H), 4.64 (ABq, J = 12.5 Hz, A =- 0.14, 2H), 5.08 (d, J = 3.7 Hz, 1H), 5.28 (d, J WO 00/31096 PCT/US99/27828 - 47 = 5.1 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.55 (d, J = 2.9 Hz, 1H), 5.77 (d, J = 6.2 Hz, 1H), 7.18 (dd, J = 1.5, 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.62-7.68 (m, 2H), 7.98 (dd, J = 1.5, 8.3 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3450, 3380, 3320, 2920, 2880, 2240, 1725, 1710, 1670, 1610, 1590, 1530, 1440, 1420, 1370, 5 1310, 1275, 1125, 1100, 1060, 1030, 1020, and 720 cm-; mass spectrum [(-) FAB], m/z 691 (M - H); Anal. Calcd. for C 32

H

37 C1N 2 0 13 : C, 55.45; H, 5.38; N, 4.04, Found: C, 55.25; H, 5.44; N, 3.90. Example 20 10 N-1 2-Chloro-5-[(4'.6'-O-((1R)-3-ethoxy-propylidene)-p-D-maltosyloxy)-methyl] phenyl }-acetamide The title compound was prepared as a white solid (0.080 g, 14%) from N-[2 chloro-5-(p-D-maltosyl-oxymethyl)-phenyl]-acetamide using 3-chloropropionalde hyde diethyl acetal and the procedure of Example 10, mp 149.5-153 oC; 1 H NMR 15 (DMSO-d) a 1.08 (t, J = 7.0 Hz, 3H), 1.70-1.81 (m, 2H), 2.07 (s, 3H), 2.44-2.54 (m, 2H), 3.04-3.17 (m, 2H), 3.24-3.60 (m, 10H), 3.64-3.71 (m, 1H), 3.95 (dd, J = 4.8, 9.9 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.63 (dd, J = 5.7, 9.7 Hz, 2H), 4.67 (ABq, J = 12.3 Hz, A6 = 0.22, 2H), 5.09 (d, J = 3.7 Hz, 1H), 5.19 (d, J = 5.3 Hz, 1H), 5.23 (d, J = 5.3 Hz, 1H), 5.46 (d, J = 3.3 Hz, 1H), 5.56 (d, J = 6.6 Hz, 1H), 7.22 (dd, J = 1.8, 20 8.1 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 9.51 (s, 1H); IR (KBr) 3500, 3420, 2970, 2920, 2840, 1690, 1590, 1530, 1440, 1420, 1370, 1320, 1250, 1110, 1070, and 1020 cm'; mass spectrum [(-) FAB], m/z 606 (M - H); Anal. Calcd. for

C

2 6

H

38 C1NO 13 -1.5 H~,O: C, 49.17; H, 6.51; N, 2.21, Found: C, 48.89; H, 5.93; N, 2.27. 25 Example 21 N- { 5- { [6-0-Benzovyl-4',6'-O-(( 1R)-3-ethoxvpropy1idene)-p-D-maltosyloxvyl-methyl } 2-chloro-phenvyl I -acetamide The title compound was prepared as a off-white solid (0.015 g, 26%) from N 30 { 2-chloro-5-[(4',6'-O-((1R)-3-ethoxy-propylidene)-3-D-maltosyloxy)-methyl] phenyl}-acetamide using the procedure of Example 2, mp >94 oC (decomp.); 'H NMR (DMSO-d) 8 1.07 (t, J = 7.0 Hz, 3H), 1.69-1.78 (m, 2H), 2.04 (s, 3H), 2.44- WO 00/31096 PCT/US99/27828 - 48 2.54 (m, 2H), 3.09 (t, J = 9.7 Hz, 1H), 3.14-3.21 (m, 1H), 3.26-3.42 (m, 4H), 3.45 3.60 (m, 4H), 3.71-3.76 (m, 1H), 3.91 (dd, J = 4.4, 9.7 Hz, 1H), 4.30 (dd, J = 5.3, 12.3 Hz, 1H), 4.37 (d, J = 7.7 Hz, 1H), 4.54-4.61 (m, 2H), 4.64 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 5.07 (d, J = 4.0 Hz, 1H), 5.25 (d, J = 5.3 Hz, 1H), 5.34 (d, J = 5.3 Hz, 5 1H), 5.55 (d, J = 2.6 Hz, 1H), 5.77 (d, J = 6.2 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.62-7.68 (m, 2H), 7.98 (d, J = 7.2 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3410, 2910, 2850, 1720, 1670, 1590, 1530, 1440, 1420, 1370, 1280, 1115, 1060, 1025, and 720 cm'; mass spectrum [(+) FAB], m/z 734 (M + Na)*; Anal. Calcd. for C 33

H

42 CINO 4 .4.0 H20: C, 50.54; H, 6.43; N, 1.79, Found: 10 C, 50.22; H, 5.28; N, 1.77. Example 22 N-(2-Chloro-5- {[4'.6'-O-(4-pvridinemethylidene)-3-D-maltosyll-oxy-nethyl _1 phenvl)-acetamide 15 To a stirred solution of N-[ 2 -chloro-5-(p-D-maltosyl-oxymethyl)-phenyl] acetamide (0.500 g, 0.954 mmol) in DMF (25 mL) at rt was added 4 pyridinecarboxaldehyde (0.446 mL, 4.67 mmol) followed by concentrated HSO 4 (0.105 mL, 3.78 mmol). The reaction mixture was heated to 110 oC for 18 h. The reaction was then quenched with K 2 CO, (1.40 g, 10.1 mmol) with an additional 0.5 h 20 heating at 60 oC. At this point, the solution was filtered hot, and the solvent was distilled off using the high vac. The residue was purified by flash chromatography (80:6:3 to 5:2:1 EtOAc:EtOH:H O gradient) to afford the product (0.050 g, 9%) as a yellow solid, mp >112 oC (decomp.); 'H NMR (DMSO-d) 6 2.07 (s, 3H), 3.05-3.13 (m, 1H), 3.27-3.49 (m, 4H), 3.49-3.62 (m, 3H), 3.66-3.75 (m, 3H), 4.14 (dd, J = 25 12.5, 17.5 Hz, 1H), 4.29 (d, J = 7.7 Hz, 1H), 4.67 (t, J = 5.9 Hz, 1H), 4.67 (ABq, J = 12.3 Hz, A6 = 0.22, 2H), 5.16 (d, J = 3.7 Hz, 1H), 5.25 (d, J = 5.3 Hz, 1H), 5.35 (d, J = 4.8 Hz, 1H), 5.50 (d, J = 3.3 Hz, 1H), 5.61-5.65 (m, 2H), 7.22 (dd, J = 1.8, 8.3 Hz, 1H), 7.42-7.47 (m, 3H), 7.65 (s, 1H), 8.60 (d, J = 5.9 Hz, 2H), 9.52 (s, 1H); IR (KBr) 3390, 2920, 2830, 1670, 1620, 1590, 1530, 1450, 1420, 1380, 1310, 1270, 1245, 30 1180, 1145, 1075, 1055, 1030, and 755 cm'; mass spectrum [(-) FAB], m/z 611 (M H); Anal. Calcd. for C 27

H

33 C1N 2 0,, - 4.25 HO0: C, 47.03; H, 6.07; N, 4.06, Found: C, 46.63; H, 5.00; N, 3.60.

WO 00/31096 PCT/US99/27828 - 49 Example 23 Benzoic acid 6-(3-acetvlamino-4-chloro-benzoyloxy)-3-(7,8-dihydroxv-2-pyridin-4 vl-hexahydro-pyrano f3,2-d [ 1.31 dioxin-6-vloxy)-4.5-dihydroxv-tetrahvdro-pyran-2 5 vlmeth1yl ester The title compound was prepared as a off-white solid (0.025 g, 46%) from N (2-chloro-5- { [4',6'-O-(4-pyridinemethylidene)-p3-D-maltosyl]-oxy-methyl }-phenyl) acetamide using the procedure of Example 2, mp 260-261.5 oC; 'H NMR (DMSO-d) 8 2.04 (s, 3H), 3.15-3.22 (m, 1H), 3.25-3.43 (m, 2H), 3.51 (td, J = 2.9, 8.8 Hz, 1H), 10 3.55-3.64 (m, 3H), 3.68-3.77 (m, 2H), 4.07 (dd, J = 4.6, 9.7 Hz, 1H), 4.34 (dd, J = 5.3, 12.3 Hz, 1H), 4.39 (d, J = 7.7 Hz, 1H), 4.56-4.62 (m, 1H), 4.65 (ABq, J = 12.3 Hz, A6 = 0.14, 2H), 5.15 (d, J = 4.0 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.39 (d, J = 5.1 Hz, 1H), 5.56 (d, J = 3.1 Hz, 1H), 5.58 (s, 1H), 5.79 (d, J = 6.2 Hz, 1H), 7.18 (dd, J = 2.0, 8.3 Hz, 1H), 7.38-7.45 (m, 3H), 7.53 (t, J = 7.9 Hz, 2H), 7.62-7.68 (m, 2H), 15 7.97-8.01 (m, 2H), 8.59 (d, J = 4.6 Hz, 2H), 9.49 (s, 1H); IR (KBr) 3460, 3310, 3240, 2910, 2830, 1725, 1665, 1620, 1590, 1530, 1420, 1375, 1275, 1140, 1075, 1055, 1030, and 715 cm'; mass spectrum [(+) FAB], m/z 717 (M + H)*, 739 (M + Na)*; Anal. Calcd. for C 34H37C1N20,3 - 1.5 HO: C, 54.88; H, 5.42; N, 3.76, Found: C, 54.55; H, 4.98; N, 3.68. 20 Example 24 N-{ 5-r(4'.6'- O-Benzvlidene- -D-maltosyloxy)-methyl]l-2-chloro-phenvyI I-acetamide To a stirred solution of N-[2-chloro-5-(p-D-maltosyl-oxymethyl)-phenyl] acetamide (14.15 g, 27.0 mmol) in DMF (325 mL) at rt was added benzaldehyde 25 dimethyl acetal (8.11 mL, 54.0 mmol) dropwise followed by TsOH.H 2 0 (2.57 g, 13.5 mmol). The reaction mixture was heated to 60 oC for 6 h and then quenched with

KCO

3 (1.87 g, 13.5 mmol) with an additional 0.5 h heating at this temperature. At this point, the solution was filtered hot, and the solvent was distilled off using the high vac. The residue was purified by flash chromatography (80:2:1 to 20:2:1 30 EtOAc:EtOH:H 2 0 gradient) to afford the product (10.8 g, 65%) as a white solid, mp 143-147 'C; 'H NMR (DMSO-d) 8 2.08 (s, 3H), 3.07-3.12 (m, 1H), 3.28-3.50 (m, 5H), 3.51-3.60 (m, 2H), 3.64-3.75 (m, 3H), 4.10-4.12 (m, 1H), 4.30 (d, J = 7.9 Hz, WO 00/31096 PCT/US99/27828 - 50 1H), 4.67 (t, 5.9 Hz, 1H), 4.68 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.25 (d, J = 5.1 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 5.51 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.63 ( d, J = 6.8 Hz, 1H), 7.22 (dd, J = 1.5, 8.3 Hz, 1H), 7.35-7.38 (m, 3H), 7.42-7.46 (m, 3H), 7.66 (s, 1H), 9.53 (s, 1H); IR (KBr) 3500, 3410, 2910, 2850, 5 1700, 1600, 1550, 1440, 1425, 1375, 1310, 1230, 1150, 1070, and 1030 cm'; mass spectrum [(+) FAB], m/z 634 (M + Na)'; Anal. Calcd. for C 28

H

34 C1NO 1 2 1.0 H 2 0: C, 53.38; H, 5.76; N, 2.22, Found: C, 53.58; H, 5.62; N, 2.25. Example 25 10 N-f{ 5-[(4',6' -O-Benzylidene-2.2',3,3',6-penta-O-acetvyl--D-maltosyl-oxy)-methvll-2 chloro-phenvyl I -acetamide To a stirred solution of N-{5-[(4',6'-O-benzylidene-3-D-maltosyloxy) methyl]-2-chloro-phenyl}-acetamide (0.230 g, 0.376 mmol) and triethylamine (0.576 mL, 4.14 mmol) in DMF (5 mL) at rt was added dropwise acetic anhydride (0.195 15 mL, 2.07 mmol) followed by a catalytic amount of DMAP (0.023 g, 0.188 mmol). After 18 h, the mixture was concentrated, and the resulting residue was diluted with EtOAc (100 mL). This layer was washed with 1 N HC1 (10 mL), sat. aq. NaHCO 3 (10 mL), and brine (10 mL) and then dried (Na 2

SO

4 ). After concentration, the residue was purified by flash chromatography (10:90 to 80:20 EtOAc:petroleum ether gradient) to 20 afford the product (0.181 g, 59%) as an off-white solid, mp 99-102 oC; 'H NMR (DMSO-d) a 1.92 (s, 3H), 1.94 (s, 3H), 1.97 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.08 (s, 3H), 3.67-3.75 (m, 1H), 3.89 (t, J = 9.4 Hz, 1H), 3.95-4.04 (m, 3H), 4.12-4.19 (m, 2H), 4.39 (dd, J = 1.5, 11.9 Hz, 1H), 4.54 (d, J = 12.7 Hz, 1H), 4.68-4.74 (m, 2H), 4.85-4.89 (m, 2H), 5.24 (t, J = 10.1 Hz, 1H), 5.28 (d, J = 4.0 Hz, 1H), 5.32 (d, J = 9.4 25 Hz, 1H), 5.62 (s, 1H), 7.07 (dd, J = 1.8, 8.1 Hz, 1H), 7.36 (s, 5H), 7.45 (d, J = 8.3 Hz, 1H), 7.62 (s, 1H), 9.50 (s, 1H); IR (KBr) 3390, 2920, 2850, 1755, 1690, 1600, 1530, 1410, 1375, 1230, and 1050 cm-'; mass spectrum [(+) FAB], m/z 822 (M + H)', 844 (M + Na)*; Anal. Calcd. for C 38

,H

44 C1NO 1 7 1.0 H 2 0: C, 54.32; H, 5.52; N, 1.67, Found: C, 54.68; H, 5.44; N, 1.57. 30 WO 00/31096 PCT/US99/27828 -51 Example 26 N- 5-[(6-O-Benzoyl-4',6'-O-benzvlidene- B-D-maltosyl-oxy)-methyll-2-chloro phenylv }-acetamide The title compound was prepared as a white solid (4.04 g, 69%) from N-{5 5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using a procedure similar to Example 2, mp 185-187 oC; 'H NMR (DMSO-d) 6 2.05 (s, 3H), 3.16-3.22 (m, 1H), 3.32-3.42 (m, 2H), 3.48-3.64 (m, 4H), 3.71 (dd, J = 4.8, 9.7 Hz, 1H), 3.74-3.79 (m, 1H), 4.05 (dd, J = 4.8, 10.3 Hz, 1H), 4.35 (dd, J = 5.3, 12.3 Hz, 1H), 4.39 (d, J = 7.7 Hz, 1H), 4.58-4.63 (m, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.14, 10 2H), 5.14 (d, 4.0 Hz, 1H), 5.34 (t, J = 5.1 Hz, 2H), 5.52 (s, 1H), 5.57 (d, J = 3.1 Hz, 1H), 5.79 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 2.0, 8.3 Hz, 1H), 7.32-7.38 (m, 3H), 7.38 7.45 (m, 3H), 7.51-7.55 (m, 2H), 7.63-7.68 (m, 2H), 7.98-8.01 (m, 2H), 9.49 (s, 1H); IR (KBr) 3380, 3290, 2890, 2870, 1730, 1670, 1600, 1540, 1440, 1420, 1375, 1275, 1070, 1050, 1025, 975, and 710 cm-'; mass spectrum [(+) FAB], m/z 716/718 (M + 15 H)+, 738/740 (M + Na)*; Anal. Calcd. for C 3 5

,H

38 C1NO 3 : C, 58.70; H, 5.35; N, 1.96, Found: C, 58.53; H, 5.36; N, 1.94. Example 27 (R)-N-[2-Chloro-5-r[[2.3-di-O-acetyl-6-O-benzovyl-4-O-[ 2,3-di-O-acetyl-4.6-O 20 (phenvlmethylene)-(-D- lucopvranovsl]-B-D- glucopvranosylloxyl-methyll phenyl acetamide The title compound was prepared as a glassy white solid (0.048 g, 86%) from N-{ 5-[(6-O-benzoyl-4',6'-O-benzylidene-p-D-maltosyl-oxy)-methyl]-2-chloro phenyl}-acetamide using a procedure similar to Example 25, mp 101-104 oC; 'H 25 NMR (DMSO-d) 8 1.94 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.05 (s, 3H), 3.61 (t, J = 9.7 Hz, 1H), 3.70-3.76 (m, 1H), 3.80 (dd, J = 4.6 Hz, 1H), 3.86 (t, J = 9.4 Hz, 1H), 4.13-4.22 (m, 2H), 4.46 (dd, J = 3.7, 12.5 Hz, 1H), 4.64 (ABq, J = 12.7 Hz, A6 = 0.14, 2H), 4.68 (d, J = 10.5 Hz, 1H), 4.79 (dd, J = 8.1, 9.4 Hz, 1H), 4.87-4.91 (m, 2H), 5.27 (t, J = 9.9 Hz, 1H), 5.33-5.38 (m, 2H), 5.54 (s, 1H), 7.04 (dd, J= 1.8, 30 8.1 Hz, 1H), 7.28-7.36 (m, 5H), 7.41 (d, J = 8.3 Hz, 1H), 7.52-7.57 (m, 2H), 7.61 (s, 1H), 7.65-7.71 (m, 1H), 8.03-8.07 (m, 2H), 9.48 (s, 1H); IR (KBr) 3400, 2950, 2850, 1755, 1600, 1540, 1440, 1420, 1375, 1240, 1070, and 1030 cm'; mass spectrum [(+) WO 00/31096 PCT/US99/27828 - 52 FAB], m/z 884 (M + H)+, 906 (M + Na)*; Anal. Calcd. for C 43 H46C1NO 1 7 : C, 58.41; H, 5.24; N, 1.58, Found: C, 58.24; H, 5.31; N, 1.59. Example 28 5 (R)-N-[2-Chloro-5-[[[6-O-(5-methoxy-1,5-dioxopentvl)-4-O-[4,6-O (phenylmethylene)-a-D- glucopvranovsl]- p-D- elucopyranosyl] oxymethyll pheny1] acetamide The title compound was prepared as a white foam (0.149 g, 50%) from N-{5 [(4',6'-O-benzylidene-p3-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 10 methyl-4-(chloroformyl)-butyrate as the acid chloride and a procedure similar to Example 2, mp 79-81 oC; 'H NMR (CDC13) 8 1.90-1.98 (m, 2H), 2.13 (s, 3H), 2.35 2.43 (m, 4H), 3.41 (t, J = 9.4 Hz, 1H), 3.47-3.73 (m, 6H), 3.65 (s, 3H), 3.82-3.89 (m, 2H), 3.93 (t, d = 9.4 Hz, 1H), 4.06-4.26 (bs, 1H), 4.20 (dd, J = 4.6, 12.3 Hz, 1H), 4.28 (q, J = 5.1, 10.5 Hz, 1H), 4.34-4.40 (m, 2H), 4.70 (ABq, J = 12.5 Hz, AS = 0.23, 15 2H), 4.76-4.94 (bs, 1H), 5.04 (d, J = 4.0 Hz, 1H), 5.20-5.36 (bs, 1H), 5.47 (s, 1H), 7.01 (dd, J = 1.8, 8.6 Hz, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.33-7.35 (m, 3H), 7.46-7.48 (m, 2H), 7.64 (s, 1H), 8.32 (s, 1H); IR (KBr) 3400, 2930, 2880, 1735, 1600, 1540, 1450, 1420, 1375, 1310, 1250, 1200, 1160, 1070, and 1025 cm'; mass spectrum [(+) FAB], m/z 740 (M + H)+, 762 (M + Na)*; Anal. Calcd. for C 34

H

42 C1NO,15 * 1.0 H,0: 20 C, 53.86; H, 5.85; N, 1.85, Found: C, 53.51; H, 5.80; N, 1.73. Example 29 4-Chloro-3-nitro-benzyl-4'.6'-O-benvzlidene- -D-maltoside step 1 25 4-Chloro-3-nitro-benzyl-p-D-maltoside The title compound was prepared as a yellow powder (1.04 g, 97%) from 4 chloro-3-nitro-benzyl- P3-D-maltoside heptaacetate using a procedure similar to step 4 of Example 1, mp 168-169 oC; 'H NMR (DMSO-d) 8 3.03-3.13 (m, 2H), 3.20-3.38 (m, 4H), 3.41-3.49 (m, 3H), 3.55-3.64 (m, 2H), 3.68-3.75 (m, 1H), 4.00-5.50 (bs, 30 7H), 4.31 (d, J = 7.7 Hz, 1H), 4.79 (ABq, J = 13.6 Hz, AS = 0.17, 2H), 5.00 (d, J = 3.7 Hz, 1H), 7.70-7.78 (m, 2H), 8.09 (d, J = 1.8 Hz, 1H); IR (KBr) 3380, 2900, 1720, 1625, 1550, 1365, 1140, 1080, and 1030 cm-'; mass spectrum [(+) FAB], m/z 533/535 WO 00/31096 PCT/US99/27828 - 53 (M + Na)'; Anal. Calcd. for C,19H 26 C1NO3 * 1.0 H 2 0: C, 43.07; H, 5.33; N, 2.64, Found: C, 43.11; H, 5.23; N, 2.58. step 2 5 4-Chloro-3-nitro-benzyl-4',6'-O-benyzlidene-p-D-maltoside The title compound was prepared as a yellow solid (0.869 g, 74%) from 4 chloro-3-nitro-benzyl-p-D-maltoside using a procedure similar to Example 24, mp >122 oC (decomp.); 'H NMR (DMSO-d) 6 3.11 (dd, J = 4.8, 8.8 Hz, 1H1), 3.30-3.42 (m, 4H), 3.46 (dd, J = 3.3, 9.0 Hz, 1H), 3.49-3.60 (m, 2H), 3.64-3.75 (m, 3H), 4.12 10 (dd, J = 2.9, 8.1 Hz, 1H), 4.33 (d, J = 7.7 Hz, 1H1), 4.65 (t, J = 5.7 Hz, 1H), 4.80 (ABq, J = 13.6 Hz, A6 = 0.16, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.29 (d, J = 5.1 Hz, 1H1), 5.34 (d, J = 5.1 Hz, 1H), 5.53 (d, J = 3.1 Hz, 1H), 5.57 (s, 1H), 5.62 (d, J = 6.6 Hz, 1H), 7.34-7.38 (m, 3H), 7.42-7.46 (m, 2H), 7.70-7.77 (m, 2H), 8.10 (d, J = 1.6 Hz, 1H); IR (KBr) 3390, 2920, 2870, 1625, 1610, 1590, 1550, 1440, 1420, 1360, 1200, 15 1140, 1070, and 1030 cm'; mass spectrum [(+) FAB], m/z 600/602 (M + H)', 622/624 (M + Na)'; Anal. Calcd. for C 26 H3oC1NO,13 * 0.5 H20: C, 51.28; H, 5.13; N, 2.30, Found: C, 51.13; H, 5.21; N, 2.30. Example 30 20 4-Chloro-3-nitro-benzyl-6-O-benzovl-4',6'-O-benvzlidene-p-D-maltoside The title compound was prepared as a off-white glass (0.155 g, 49%) from 4 chloro-3-nitro-benzyl-4',6' -O-benyzlidene-p1-D-maltoside using a procedure similar to Example 2, mp 111-114 oC; 'H NMR (DMSO-d) 8 3.19-3.26 (m, 1H), 3.28-3.43 (m, 2H), 3.51-3.65 (m, 4H), 3.68-3.75 (m, 1H), 3.77-3.81 (m, 1H1), 4.04 (dd, J = 4.6, 9.9 25 Hz, 1H1), 4.34 (dd, J = 5.1, 12.3 Hz, 1H1), 4.45 (d, J = 7.9 Hz, 1H), 4.59 (d, J = 12.3 Hz, 1H1), 4.79 (ABq, J = 13.6 Hz, A6 = 0.10, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.46 (d, J = 5.1 Hz, 1H), 5.52 (s, 1H), 5.60 (d, J = 3.1 Hz, 1H), 5.80 (d, J = 6.2 Hz, 1H11), 7.33-7.37 (m, 3H), 7.39-7.43 (m, 2H), 7.50-7.55 (m, 2H), 7.63 7.68 (m, 1H1), 7.68-7.73 (m, 2H), 7.97 (dd, J = 1.1, 8.1 Hz, 2H), 8.08 (s, 1H); IR 30 (KBr) 3400, 2910, 2860, 1725, 1610, 1540, 1440, 1360, 1325, 1275, 1070, and 1025 cm- ; mass spectrum [(+) FAB], m/z 704 (M + H)+, 726 (M + Na)*; Anal. Calcd. for WO 00/31096 PCT/US99/27828 - 54 C 3 3

H

34 C1NO 14 . 1.0 H 2 0: C, 54.89; H, 5.03; N, 1.94, Found: C, 54.72; H, 4.56; N, 1.91. Example 31 5 (R)-(4-Chloro-3-nitrophenvyl)methyl-2,3-di-O-acetv1-6-O-benzovl-4-O-[2,3-di-0 acetyl-4,6-O-(phenyl1methylene)-a-D-glucopvranosyll-3-D- glucopvranoside The title compound was prepared as a off-white solid (0.0773 g, 84%) from 4 chloro-3-nitro-benzyl-6-O-benzoyl-4',6'-O-benyzlidene-p3-D-maltoside using a procedure similar to Example 25, mp 138-140 oC; 'H NMR (DMSO-d) 8 1.95 (s, 10 3H), 1.96 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 3.61 (t, J = 9.4 Hz, 1H), 3.69-3.77 (m, 1H), 3.79 (dd, J = 4.6, 9.4 Hz, 1H), 3.86 (t, J = 9.4 Hz, 1H), 4.13-4.25 (m, 2H), 4.44 (dd, J = 3.5, 12.3 Hz, 1H), 4.66-4.69 (m, 1H), 4.71 (d, J = 13.6 Hz, 1H), 4.80-4.84 (m, 2H), 4.89 (dd, J = 4.2, 10.3 Hz, 1H), 4.96 (d, J = 7.9 Hz, 1H), 5.27 (t, J = 9.9 Hz, 1H), 5.34-5.40 (m, 2H), 5.54 (s, 1H), 7.27-7.37 (m, 5H), 7.51-7.56 (m 2H), 7.57 (dd, 15 J = 2.0, 8.3 Hz, 1H), 7.65-7.70 (m, 1H), 7.72 (d, J = 8.3 Hz, 1H), 7.93 (d, J = 2.0 Hz, 1H), 8.01-8.05 (m, 2H); IR (KBr) 3440, 2950, 2830, 1755, 1620, 1550, 1440, 1410, 1370, 1320, 1240, 1160, 1120, 1070, 1030, and 990 cm'; mass spectrum [(+) FAB], m/z 872 (M + H)+, 894 (M + Na)+; Anal. Calcd. for C 41

H

42 CINO, - 0.5 H 2 0: C, 55.88; H, 4.92; N, 1.59, Found: C, 55.90; H, 4.80; N, 1.56. 20 Example 32 Nicotinic acid 6-(4-chloro-3-nitro-benzyloxy)-3-(7,8-dihydroxy-2-phenyl-hexahydro pyrano r3,2-d][ 1,3] dioxin-6-vloxy)-4,5-dihydroxv-tetrahydro-pyran-2-ylmethvl ester The title compound was prepared as a white foam (0.211 g, 45%) from 4 25 chloro-3-nitro-benzyl-4',6'-O-benyzlidene-p-D-maltoside using nicotinoyl chloride hydrochloride and a procedure similar to Example 2 (except compound purified directly with flash chromatography), mp >105 oC (decomp.); 'H NMR (DMSO-d) a 3.21-3.28 (m, 1H), 3.32-3.42 (m, 2H), 3.51-3.60 (m, 3H), 3.65 (t, J = 9.2 Hz, 1H), 3.67-3.74 (m, 1H), 3.78-3.83 (m, 1H), 4.01-4.06 (m, 1H), 4.38 (dd, J = 5.1, 12.3 Hz, 30 1H), 4.45 (d, J = 7.9 Hz, 1H), 4.58-4.64 (m, 1H), 4.79 (ABq, J = 13.6 Hz, AS = 0.09, 2H), 5.17 (d, J = 3.7 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.46 (d, J = 5.3 Hz, 1H), 5.52 (s, 1H), 5.61 (d, J = 3.1 Hz, 1H), 5.82 (d, J = 6.2 Hz, 1H), 7.34-7.37 (m, 3H), 7.39- WO 00/31096 PCT/US99/27828 - 55 7.43 (m, 2H), 7.54-7.59 (m, 1H), 7.68-7.71 (m, 2H), 8.08 (d, J = 1.3 Hz, 1H), 8.31 (d, J = 7.9 Hz, 1H), 8.78-8.88 (bs, 1H), 9.05-9.19 (bs, 1H); IR (KBr) 3400, 2900, 2870, 1725, 1600, 1540, 1440, 1410, 1360, 1285, 1070, 1030, 740, and 690 cm'; mass spectrum [(+) FAB], m/z 705/707 (M + H)'; Anal. Calcd. for C 32

H

33 C1N 2 014. 1.0 5 HO20: C, 53.15; H, 4.88; N, 3.87, Found: C, 53.33; H, 4.78; N, 3.72. Example 33 (R)-(4-Chloro-3-nitrophenyl)methyl 4-[2,3-di-O-acetyl-4,6-O-(phenylmethylene)-a D-2lucopvranosyll-3-D-glucopyranoside 2,3-diacetate 6-(3-pyridinecarboxylate) 10 The title compound was prepared as a white foam (0.123 g, 95%) from nicotinic acid 6

-(

4 -chloro-3-nitro-benzyloxy)-3-(7,8-dihydroxy-2-phenyl-hexahydro pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2-ylmethyl ester using a procedure similar to Example 25, mp >101 oC (decomp.); 'H NMR (DMSO d6) 6 1.95 (s, 3H), 1.96 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 3.64 (t, J = 9.4 Hz, 1H), 15 3.69-3.81 (m, 2H), 3.87 (t, J = 9.4 Hz, 1H), 4.17 (dd, J = 3.1, 5.7 Hz, 1H), 4.27 (t, J = 9.4 Hz, 1H), 4.47 (dd, J = 4.0, 12.5 Hz, 1H), 4.69-4.75 (m, 2H), 4.80-4.91 (m, 3H), 4.96 (d, J = 8.1 Hz, 1H), 5.26 (t, J = 10.1 Hz, 1H1), 5.33-5.39 (m, 2H), 5.55 (s, 1H), 7.29-7.36 (m, 5H), 7.55-7.59 (m, 2H1), 7.72 (d, J = 8.3 Hz, 1H), 7.93 (d, J = 2.0 Hz, 1H), 8.36 (dt, J = 2.2, 7.9 Hz, 1H), 8.84 (dd, J = 1.8, 4.8 Hz, 1H), 9.16 (dd, J = 0.9, 20 2.2 Hz, 1H); IR (KBr) 3440, 2930, 2860, 1755, 1600, 1540, 1420, 1375, 1280, 1240, 1140, 1070, 1060, 1030, and 995 cm-'; mass spectrum [(+) FAB], m/z 873/875 (M + H)', 895/897 (M + Na)'; Anal. Calcd. for C 40

H

4 xC1N 2 0 1 8 , - 1.25 HO20: C, 53.64; H, 4.89; N, 3.13, Found: C, 53.46; H, 4.51; N, 2.96. 25 Example 34 4-Methoxy-benzoic acid 6-(3-acetylamino-4-chloro-benzvloxy)-3-(7,8-dihydroxy-2 phenvyl-hexahydro-pyrano [3,2-dI[ 1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro pyran-2-ylmethyl ester The title compound was prepared as a white foam (0.284 g, 47%) from N-{5 30 [(4',6'-O-benzylidene-0-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using p-anisoyl chloride and a procedure similar to Example 2, mp >117 oC (decomp.); 'H NMR (DMSO-d) 8 2.05 (s, 3H), 3.15-3.21 (m, 1H), 3.35 (d, J = 9.4 Hz, 1H), 3.35- WO 00/31096 PCT/US99/27828 - 56 3.42 (m, 1H), 3.48-3.61 (m, 4H), 3.67-3.76 (m, 2H), 3.82 (s, 3H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H), 4.29 (dd, J = 5.5, 12.3 Hz, 1H), 4.38 (d, J = 7.9 Hz, 1H), 4.55-4.60 (m, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 5.13 (d, J = 3.7 Hz, 1H), 5.34 (dd, J = 4.0, 5.3 Hz, 2H), 5.52 (s, 1H), 5.56 (d, J = 2.9 Hz, 1H), 5.77 (d, J = 6.2 Hz, 1H), 5 7.02-7.06 (m, 2H), 7.19 (dd, J = 2.0, 8.3 Hz, 1H), 7.33-7.37 (m, 3H), 7.39-7.44 (m, 3H), 7.64 (s, 1H), 7.94 (dt, J = 2.9, 9.9 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3410, 3000, 2910, 2880, 1720, 1610, 1580, 1530, 1515, 1450, 1420, 1375, 1255, 1160, 1070, and 1025 cm'; mass spectrum [(+) FAB], m/z 746/748 (M + H)+, 768/770 (M + Na), 784/786 (M + K)+; Anal. Calcd. for C 36

H

40 C1N0 1 4 * 2.0 H,0: C, 55.28; H, 5.67; N, 10 1.79, Found: C, 55.38; H, 5.28; N, 1.72. Example 35 4-Methoxv-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzvloxy)-3-(7,8 diacetoxy-2-phenvl-hexahydro-pyrano [3,2-dI [ 1,31 dioxin-6-yloxy)-tetrahydro-pyran 15 2-v1methyl ester The title compound was prepared as a white foam (0.142 g, 81%) from 4 methoxy-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro 20 pyran-2-ylmethyl ester using a procedure similar to Example 25, mp >110 oC (decomp.); 'H NMR (DMSO-d) 6 1.94 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 1. 99 (s, 3H), 2.06 (s, 3H), 3.61 (t, J = 9.7 Hz, 1H), 3.68-3.75 (m, 1H), 3.80 (dd, J = 4.6, 9.4 Hz, 1H), 3.82 (s, 3H), 3.82-3.89 (m, 1H), 4.11-4.16 (m, 1H), 4.17 (q, 9.7 Hz, 1H), 4.40 (dd, J = 3.3, 12.3 Hz, 1H), 4.63 (ABq, J = 12.7 Hz, AS = 0.15, 2H), 4.64 (d, J = 25 10.8 Hz, 1H), 4.77 (dd, J = 7.9, 9.4 Hz, 1H), 4.86-4.91 (m, 2H), 5.26 (t, J = 9.9 Hz, 1H), 5.32-5.38 (m, 2H), 5.54 (s, 1H), 7.06 (dt, J = 2.9, 9.7 Hz, 3H), 7.29-7.37 (m, 5H), 7.42 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 7.99 (dt, J = 2.9, 9.9 Hz, 2H), 9.49 (s, 1H); IR (KBr) 3400, 2950, 2840, 1755, 1700, 1600, 1580, 1535, 1515, 1450, 1420, 1375, 1240, 1165, 1110, 1070, 1055, and 1030 cm'; mass spectrum [(+) FAB], m/z 30 914/916 (M + H)+, 936/938 (M + Na)'; Anal. Calcd. for C 44

H

48 C1NO 8 * 1.0 HO: C, 56.68; H, 5.41; N, 1.50, Found: C, 56.37; H, 5.08; N, 1.48.

WO 00/31096 PCT/US99/27828 - 57 Example 36 4-Chloro-benzoic acid 6-(3-acetylamino-4-chloro-benzvloxy)-3-(7,8-dihvdroxv-2 phenvl-hexahydro-pyrano r3,2-d] [1,3] dioxin-6- yloxy)-4.5-dihydroxy-tetrahydro pyran-2-ylmethyl ester 5 The title compound was prepared as a white foam (0.372 g, 61%) from N-{5 [(4',6'-O-benzylidene-1-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 4-chlorobenzoyl chloride and a procedure similar to Example 2, mp >113 oC (decomp.); 'H NMR (DMSO-d 6 ) 6 2.05 (s, 3H), 3.16-3.21 (m, 1H), 3.28-3.41 (m, 2H), 3.48-3.62 (m, 4H), 3.69 (dd, J = 5.1, 9.9 Hz, 1H), 3.76 (ddd, J = 1.5, 4.6, 9.4 10 Hz, 1H), 4.04 (dd, J = 4.8, 9.9 Hz, 1H), 4.33-4.40 (m, 2H), 4.55-4.60 (m, 2H), 4.73 (d, J = 12.5 Hz, 1H), 5.13 (d, J = 4.0 Hz, 1H), 5.35 (t, J = 5.3 Hz, 2H), 5.52 (s, 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.81 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 2.0, 8.3 Hz, 1H), 7.33-7.37 (m, 3H), 7.38-7.43 (m, 3H), 7.59 (dt, J = 2.4, 9.2 Hz, 2H), 7.64 (s, 1H), 7.99 (dt, J = 2.4, 9.0 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3410, 2910, 2870, 1725, 1590, 15 1530, 1440, 1420, 1375, 1270, 1070, 1025, and 760 cm'; mass spectrum [(+) FAB], m/z 750/752/754 (M + H)+, 772 (M + Na)*, 788/790/792 (M + K)+; Anal. Calcd. for

C

35

H

37 C1 2

NO,

3 1.5 H2O: C, 54.06; H, 5.18; N, 1.80, Found: C, 53.76; H, 4.78; N, 1.77. 20 Example 37 4-Chloro-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 diacetoxy-2-phenyl-hexahvdro-pyran o [3,2-di [1,3] dioxin-6-v1oxy)-tetrahvdro-pvran 2-ylmeth1yl ester The title compound was prepared as a white foam (0.225 g, 72%) from 4 25 chloro-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro pyran-2-ylmethyl ester using a procedure similar to Example 25, mp 114-115 oC; 'H NMR (DMSO-d) 8 1.94 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.05 (s, 3H), 3.62 (t, J = 9.2 Hz, 1H), 3.68-3.74 (m, 1H), 3.79 (dd, J = 4.2, 9.2 Hz, 1H), 3.86 (t, J = 30 9.4 Hz, 1H), 4.13-4.19 (m, 1H), 4.18 (q, J = 9.4, 1H), 4.47 (dd, J = 3.5, 12.3 Hz, 1H), 4.63 (ABq, J = 12.7 Hz, A6 = 0.14, 2H), 4.66 (d, J = 10.8 Hz, 1H), 4.79 (dd, J = 8.1, 9.2 Hz, 1H), 4.86-4.91 (m, 2H), 5.26 (t, J = 9.9 Hz, 1H), 5.32-5.38 (m, 2H), 5.54 (s, WO 00/31096 PCT/US99/27828 - 58 1H), 7.05 (dd, J = 1.8, 8.3 Hz, 1H), 7.27-7.31 (m, 2H), 7.32-7.36 (m, 3H), 7.42 (d, J = 8.3 Hz, 1H1), 7.58-7.63 (m, 3H), 8.02-8.06 (m, 2H), 9.49 (s, 1H); IR (KBr) 3410, 2950, 2860, 1755, 1690, 1600, 1530, 1450, 1420, 1375, 1260, 1140, 1070, 1055, and 1030 cm'; mass spectrum [(+) FAB], m/z 918/920/922 (M + H)+, 940/942/944 (M + 5 Na); Anal. Calcd. for C 43 H4 5 Cl 2

NO,

17 - 1.0 H20: C, 55.13; H, 5.06; N, 1.50, Found: C, 54.77; H, 4.73; N, 1.45. Example 38 (R)-N-[2-Chloro-5-[[[6-O -(4-chloro-3-nitrobenzovl)-4-O-[4,60-(phenvylmethylene) 10 a-D-glucopvranosyll- -D-glucopvranosyl] oxylvmethyl]phenyllacetamide The title compound was prepared as a white solid (0.158 g, 52%) from N-{5 [(4',6'- O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 4-chloro-3-nitrobenzoyl chloride and a procedure similar to Example 2; 'H NMR (DMSO-d 6 ) 8 2.13 (s, 3H), 3.41 (apparant t, J = 9.4 Hz, 1H), 3.55-3.69 (m, 6H), 3.77 15 (apparant t, J = 9.0 Hz, 1H), 3.87-3.97 (m, 3H1), 4.29 (dd, J = 10.5, 4.8 Hz, 1H), 4.41 (d, J = 7.7 Hz, 1H), 4.47 (dd, J = 12.1, 5.3 Hz, 1H), 4.60 (d, J = 12.7 Hz, 2H), 4.72 (dd, J = 12.0, 2.0 Hz, 1H), 4.84 (d, J = 12.5 Hz, 1H), 5.08 (d, J = 3.7 Hz, 1H1), 5.14 (bs, 1H1), 5.47 (s, 1H), 6.99 (dd, J = 8.3, 2.0 Hz, 1H), 7.29 (d, J = 8.3 Hz, 1H1), 7.32 7.44 (m, 3H), 7.45-7.47 (m, 2H), 7.60 (s, 1H), 7.64 (d, J = 8.6 Hz, 1H), 8.16 (dd, J = 20 8.3, 2.0 Hz, 1H), 8.34 (s, 1H), 8.51 (d, J = 2.0 Hz, 1H); IR (KBr) 3400, 2900, 1750, 1660, 1275 and 1075 cm-'; mass spectrum [(+) FAB], m/z 795/797/799 (M + H)', 817/819/821 (M + Na)'; Anal. Calcd. for C 35

H

36 C1 2

N

2 0 15 1.0 H 2 0: C, 51.67; H, 4.71; N, 3.44, Found: C, 51.87; H, 4.84; N, 3.60. 25 Example 39 N- 5-[(2,2',3.-Tri-O -Acetyl-6-O -(4-chloro-3-nitrobenzovyl)-4',6'-O-(benzylidene) p-D-maltosvyl)-oxvmethyl]-2-chloro-phenvyl)-acetamide The title compound was prepared as a white solid from (R)-N-[2-chloro-5 [[[6-0 -(4-chloro-3-nitrobenzoyl)-4- O-[4,60-(phenylmethylene)-a-D 30 glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide using a procedure similar to Example 25; 'H NMR (CDC1 3 ) 8 2.04 (s, 3H), 2.05 (s, 3H), 2.06 (s, 3H1), 2.22 (s, 3H), 3.11 (d, J = 3.7 Hz, 1H), 3.62 (m, 4H), 3.81-3.99 (m, 2H), 4.29 (dd, J = WO 00/31096 PCT/US99/27828 - 59 10.3, 4.8 Hz, 1H), 4.48-4.61 (m, 3H), 4.98 (dd, J = 10.3, 3.7 Hz, 1H), 5.35 (d, J = 4.0 Hz, 1H), 5.44 - 5.52 (m, 2H), 6.99 (dd, J = 8.1, 2.0 Hz, 1H), 7.31-7.42 (m, 6H), 7.58 7.59 (m, 2H), 7.63 (d, J = 8.3 Hz, 1H), 8.14 (dd, J = 8.3, 2.0 Hz, 1H), 8.31 (bs, 1H), 8.51 (d, J = 2.0 Hz, 1H); IR (KBr) 3400, 2900, 1750, 1660, 1275 and 1075 cm'; 5 mass spectrum [(+) FAB], m/z 921/923/925 (M + H)+, 943/945/947 (M + Na)'; Anal. Calcd. for C 4 ,HC12N20,: C, 53.43; H, 4.59; N, 3.04, Found: C, 52.88; H, 5.11; N, 2.59. Example 40 10 (R)-N-[2-Chloro-5-[[[6- 0 -( 4 -cvanobenzoyl)-4-O-[4,60-(phenylmethylene)-a-D glucopyranosyl] - 3-D- glucopyranosyll oxv]methyl]phenvyl] acetamide The title compound was prepared as a white solid from N-{5-[(4',6'-O benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 4 cyanobenzoyl chloride and a procedure similar to Example 2, mp 143-145 oC; 'H 15 NMR (DMSO-d) a 2.04 (s, 3H), 3.17-3.22 (m, 2H), 3.28-3.41 (m, 3H), 3.48-3.80 (m, 5H), 4.03 (dd, J = 9.4, 5.1 Hz, 1H), 4.38-4.42 (m, 2H), 4.62 (d, J = 10.8 Hz, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.13, 2H), 5.14 (d, J = 4.80 Hz, 2H), 5.35 (apparant t, J = 5.3 Hz, 2H), 5.52 (s, 1H), 5.59 (d, J = 2.9 Hz, 1H), 5.83 (d, J = 6.0 Hz, 1H), 7.19 (dd, J = 8.3, 2.0 Hz, 1H), 7.34-7.39 (m, 3H), 7.39-7.42 (m, 2H), 7.63 (s, 1H), 8.0 (d, 20 J = 8.8 Hz, 2H), 8.13 (d, J = 8.8 Hz, 2H), 9.49 (s, 1H); IR (KBr) 3400, 2900, 1725, 1660, 1275 and 1075 cm'; mass spectrum [(-) FAB], m/z 739/741 (M - H); Anal. Calcd. for C 3 6

H

3 7 C1N 2 0, 3 0.5 H20: C, 57.64; H, 5.11; N, 3.73, Found: C, 57.47; H, 5.08; N, 3.57. 25 Example 41 (R)-N-[2-Chloro-5-[[[6-0 -(4-nitrobenzovl)-4-O-[4,60-(phenylmethylene)-X-D glucopvranosyl - B-D- lucopvranosyll] oxvlmethyl]phenyll acetamide The title compound was prepared as a white solid from N-{5-[(4',6'-O benzylidene- p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 4 30 nitrobenzoyl chloride and a procedure similar to Example 2; 'H NMR (CDC1 3 ) 8 2.14 (s, 3H), 3.41 (apparant t, J = 9.2 Hz, 1H), 3.54-3.69 (m, 5H), 3.84-3.99 (m, 5H), 4.30 (dd, J = 10.1, 5.1 Hz, 1H), 4.41 (d, J = 7.7 Hz, 1H), 4.50 (dd, J = 7.5, 4.6 Hz, 2H), WO 00/31096 PCT/US99/27828 - 60 4.72 (dd, J = 12.1, 1.3 Hz, 1H), 4.73 (ABq, J = 12.5 Hz, A6 = 0.21, 2H), 4.85 (d, J = 3.4 Hz, 2H), 5.47 (s, 1H), 6.97-7.0 (m, 1H), 7.29 (d, J = 2.9 Hz, 1H), 7.32-7.36 (m, 3H), 7.44-7.52 (m, 2H), 7.60 (bs, 1H), 8.20 (d, J = 9.0 Hz, 2H), 8.29 (d, J = 9.0 Hz, 2H), 8.36 (bs, 1H); IR (KBr) 3400, 2900, 1725, 1660, 1275 and 1075 cm-'; mass 5 spectrum [(+) FAB], m/z 761/763 (M + H)', 783/785 (M + Na)*; Anal. Calcd. for

C

3 5

H

37 C1N 2 0, 5 2.0 H 2 0: C, 52.74; H, 5.18; N, 3.51, Found: C, 52.92; H, 5.07; N, 3.45. Example 42 10 (R)-N-[2-Chloro-5- r[[[6-0 -(3-trifluoromethylbenzovyl)-4-O-[4.60-(phenyl methylene)-cx-D- lucopvranosyll-13-D- 2lucopvranosvl] oxvlmethyl1phenvllacetamide The title compound was prepared as a white solid from N-{5-[(4',6'-O benzylidene-p3-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 3-trifluoro methylbenzoyl chloride and a procedure similar to Example 2, mp 194 oC; 'H NMR 15 (CDC1 3 ) 8 2.11 (s, 3H), 3.40 (apparant t, J = 9.4 Hz, 1H), 3.53-3.68 (m, 5H), 3.77 (apparant t, J = 8.8 Hz, 1H), 3.88-3.93 (m, 2H), 3.97 (apparant t, J = 9.4 Hz, 1H), 4.30 (dd, J = 10.3, 5.1 Hz, 1H), 4.40 (d, J = 7.7 Hz, 1H), 4.71 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 4.73 (d, J = 11, Hz, 1H), 5.08 (d, J = 3.7 Hz, 2H), 5.46 (s, 1H), 6.95 (dd, J = 8.34, 1.8 Hz, 1H), 7.26 (d, J = 8.3, Hz, 1H), 7.30-7.34 (m, 3H), 7.43-7.47 (m, 20 2H), 7.60 (bt, 7 Hz, 2H), 7.81 (bd, J = 7.7 Hz, 1H), 8.22 (bd, J = 8.0 Hz, 1H), 8.32 (bd, J = 9.2 Hz, 2H); IR (KBr) 3400, 2900, 1725, 1660, 1250 and 1075 cm'; mass spectrum [(+) FAB], m/z 784/786 (M + H)+, 806/808 (M + Na)*; Anal. Calcd. for

C

3 6

H

3 9 C1NF 3 0 3 * 1.0 H20: C, 53.91; H, 4.90; N, 1.75, Found: C, 54.19; H, 4.67; N, 1.75. 25 Example 43 N-f 5-[(4',6'-O-Benzylidene-6-O-(2-iodo)-benzov1-B-D-maltosyl)-oxy-methyll-2 chloro-phenvl)-acetamide The title compound was prepared as a white solid from N-{5-[(4',6'-O 30 benzylidene- p-D-maltosyloxy)-methyl]-2-chloro-phenyl } -acetamide using o iodobenzoyl chloride and a procedure similar to Example 2, mp 140-143 oC; 'H NMR (DMSO-d 6 ) 6 2.05 (s, 3H), 3.15-3.17 (m, 1H), 3.28-3.65 (m, 6H), 3.75-3.79 WO 00/31096 PCT/US99/27828 -61 (m, 3H), 4.14 (dd, J = 9.1 Hz, 1H), 4.35 (dd, J = 12.1, 5.7 Hz, 1H), 4.40 (d, J = 7.9, 1H), 4.62 (d, J = 10.8, Hz, 1H), 4.66 (ABq, J = 12.3 Hz, A6 = 0.14, 2H), 5.15 (d, J = 4.0 Hz, 1H), 5.36 (t, J = 5.3 Hz, 2H), 5.55 (s, 1H), 5.60 (d, J = 2.64 Hz, 1H), 5.87 (d, J = 6.2 Hz, 1H), 7.18 (dd, J = 8.1, 2.00 Hz, 1H), 7.26-7.30 (m, 1H), 7.34-7.50 (m, 5 6H), 7.51-7.53 (m, 1H), 7.63 (s, 1H), 7.78 (dd, J = 7.9, 1.5 Hz, 1H), 8.02 (dd, J = 7.9, 1.1 Hz, 1H), 9.50 (s, 1H); IR (KBr) 3400, 2930, 1750, 1550, 1245 and 1075 cm'; mass spectrum [(+) ESI], m/z 842/844 (M + H)+, 859/861 (M + NH4)'; Anal. Calcd. for C 35 H 3 7 CINO13 1.0 HO: C, 48.84; H, 4.53; N, 1.66, Found: C,48.59.; H, 4.28; N, 1.58. 10 Example 44 N- { 5-[(4',6'-O-Benzylv1idene-6-O-(3-iodo)-benzoy1-B-D-maltosvyl)-oxv-methyll-2 chloro-phenv 1}-acetamide The title compound was prepared as a white solid from N-{5-[(4',6'-O 15 benzylidene-3-D-maltosyloxy)-methyl]-2-chloro-phenyl}-acetamide using m-iodo benzoyl chloride and a procedure similar to Example 2, mp 175-177 oC; 'H NMR (DMSO-d 6 ) 8 2.05 (s, 3H), 3.15-3.20 (m, 2H), 3.32-3.42 (m, 2H), 3.50-3.61 (m, 4H), 3.70-3.77 (m, 2H), 4.00-4.09 (m, 2H), 4.34 (dd, J = 12.1, 5.7 Hz, 1H), 4.40 (d, J = 7.9 Hz, 1H), 4.62 (d, J = 10.5, Hz, 1H), 4.66 (ABq, J = 12.3 Hz, A6 = 0.14, 2H), 5.14 20 (d, J = 4.0 Hz, 1H), 5.35 (apparant t, J = 5.7 Hz, 2H), 5.53 (s, 1H), 5.57 (d, J = 2.9 Hz, 1H), 5.79 (d, J = 6.4 Hz, 1H), 7.01 (dd, J = 8.3, 1.8 Hz, 1H), 7.32-7.37 (m, 3H), 7.40-7.42 (m, 2H), 7.65 (s, 1H), 7.99-8.03 (m, 2H), 8.26 (t, J = 1.8 Hz, 1H), 9.50 (s, 1H); IR (KBr) 3400, 2930, 1700, 1250 and 1075 cm'; mass spectrum [(-) FAB], m/z 840 (M - H); Anal. Calcd. for C 35 H3 7 C1N0 1 3' 1.0 H20: C, 48.88; H, 4.57; N, 1.63, 25 Found: C, 49.02; H, 4.49; N, 1.54. Example 45 N-{ 5-[(4',6'-O-Benzylidene-6-(4-iodo-benzo1y)-oxy-[-D-maltosvyl)-oxv-methyl1]-2 chloro-phenvl I -acetamide 30 The title compound was prepared as a white solid (0.410 g, 60%) from N-{5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl}-acetamide using p-iodobenzoyl chloride and a procedure similar to Example 2, mp >187 oC WO 00/31096 PCT/US99/27828 - 62 (decomp.); 1 H NMR (DMSO-d) 6 2.05 (s, 3H), 3.15-3.22 (m, 1H), 3.28-3.42 (m, 2H), 3.48-3.62 (m, 4H), 3.66-3.73 (m, 1H), 3.75 (ddd, J = 1.5, 4.8, 9.7 Hz, 1H), 4.01 4.06 (m, 1H), 4.35 (dd, J = 5.3, 12.3 Hz, 1H), 4.39 (d, J = 7.7 Hz, 1H), 4.57 (d, J = 10.3 Hz, 1H), 4.65 (ABq, J = 12.5 Hz, AS = 0.14, 2H), 5.12 (d, J = 4.0 Hz, 1H), 5.35 5 (t, J = 5.3 Hz, 2H), 5.52 (s, 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.81 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 1.8, 8.1 Hz, 1H), 7.33-7.38 (m, 3H), 7.38-7.43 (m, 3H), 7.64 (s, 1H), 7.73 (dt, J = 2.0, 8.8 Hz, 2H), 7.91 (dt, J = 2.2, 8.8 Hz, 2H), 9.50 (s, 1H); IR (KBr) 3420, 3270, 2920, 2880, 1725, 1660, 1590, 1530, 1450, 1425, 1385, 1375, 1280, 1140, 1110, 1070, 1050, 1030, 1005, and 750 cm 1 ; mass spectrum [(+) FAB], m/z 10 864/866 (M + Na)*; Anal. Calcd. for C 35

H

37 C1INO 1 3 : C, 49.93; H, 4.43; N, 1.66, Found: C, 49.65; H, 4.51; N, 1.77. Example 46 (R)-N-[-2-Chloro-5-[[[6-O-(phenylacetvyl)-4- O-[4,6- O-(phenylmethylene)-ot-D 15 glucopvranosyll- p-D- glucopvranosyl oxv]methyllphenvl] acetamide The title compound was prepared as a white glass (0.249 g, 42%) from N-{5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl } -acetamide using phenylacetyl chloride and a procedure similar to Example 2, mp >98 oC (decomp.); 1 H NMR (DMSO-d 6 ) a 2.08 (s, 3H), 3.08-3.13 (m, 1H), 3.27-3.49 (m, 4H), 3.54 (dd, 20 J = 5.3, 9.2 Hz, 1H), 3.56-3.63 (m, 2H), 3.66 (dd, J = 4.4, 9.4 Hz, 1H), 3.71 (s, 2H), 4.06 (dd, J = 4.4, 9.4 Hz, 1H), 4.12 (dd, J = 5.7, 12.3 Hz, 1H), 4.32 (d, J = 7.7 Hz, 1H), 4.37 (d, J = 11.0 Hz, 1H), 4.58 (ABq, J = 12.5 Hz, A5 = 0.16, 2H), 5.02 (d, J = 3.7 Hz, 1H), 5.32 (d, J = 5.3 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.55 (s, 1H), 5.57 (d, J = 2.9 Hz, 1H), 5.83 (6.2 Hz, 1H), 7.18-7.31 (m, 6H), 7.34-7.36 (m, 3H), 7.41-7.46 25 (m, 3H), 7.65 (s, 1H), 9.53 (s, 1H); IR (KBr) 3390, 2910, 2880, 1740, 1670, 1590, 1535, 1460, 1420, 1375, 1310, 1250, 1140, 1070, and 1025 cm 1 ; mass spectrum [(+) FAB], m/z 730/732 (M + H)+, 752/754 (M + Na)'; 768/770 (M + K)+; Anal. Calcd. for C 36 H 40 C1NO 1 3 .* 2.0 I-HLO: C, 56.43; H, 5.79; N, 1.83, Found: C, 56.62; H, 5.35; N, 1.79. 30 WO 00/31096 PCT/US99/27828 - 63 Example 47 (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-4-O-r2,3-di-O-acetyl-4,6-O-(phenyl methylene)-a-D- elucopvranosyll -6-O- (phenylacetyl)- -D- elucopyranosyll oxv]methyl]phenvyl] acetamide 5 The title compound was prepared as a white foam (0.125 g, 73%) from (R)-N [-2-chloro-5-[[[6-O-(phenylacetyl)-4-O-[4,6-O-(phenylmethylene)-a-D glucopyranosyl]l-p-D-glucopyranosyl]oxy]methyl]phenyl]acetamide using a procedure similar to Example 25, mp >98 oC (decomp.); 'H NMR (DMSO-d) 6 1.93 (s, 3H), 1.94 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 2.08 (s, 3H), 3.69-3.78 (m, 4H), 3.86-3.94 10 (m, 2H), 4.01 (ddd, J = 2.6, 4.4, 9.7 Hz, 1H), 4.10 (d, J = 5.3 Hz, 1H), 4.20 (dd, J = 5.1, 12.3 Hz, 1H), 4.44-4.50 (m, 2H), 4.63-4.70 (m, 2H), 4.83 (d, J = 8.1 Hz, 1H), 4.88 (dd, J = 4.2, 10.3 Hz, 1H), 5.21-5.27 (m, 2H), 5.30 (t, J = 9.2 Hz, 1H), 5.61 (s, 1H), 7.05 (dd, J = 1.8, 8.1 Hz, 1H), 7.19-7.30 (m, 5H), 7.35 (s, 5H), 7.45 (d, J = 8.3 Hz, 1H), 7.62 (s, 1H), 9.51 (s, 1H); IR (KBr) 3400, 3030, 2940, 2840, 1755, 1690, 15 1600, 1530, 1445, 1420, 1375, 1240, 1140, 1060, and 1030 cm"; mass spectrum [(+) FAB], m/z 898/900 (M + H)+, 920/922 (M + Na)*; Anal. Calcd. for C 44

H

4 8 C1NO,17 1.75 HO: C, 56.84; H, 5.58; N, 1.51, Found: C, 56.44; H, 5.11; N, 1.59. Example 48 20 N- { 5-[(4'.6'-O-Benzylidene-6-O-phenyl-ethyl-carboxvl--D-maltosvyl)-oxy-methyll 2-chloro-phenyl I -acetamide The title compound was prepared as a white solid (0.352 g, 63%) from N-{5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl}-acetamide using hydrocinnamoyl chloride and a procedure similar to Example 2, mp 192-193; 'H 25 NMR (DMSO-d 6 ) 6 2.06 (s, 3H), 2.66 (t, J = 7.7 Hz, 2H), 2.84 (t, J = 7.7 Hz, 2H), 3.08-3.16 (m, 1H), 3.33-3.49 (m, 4H), 3.53-3.59 (m, 2H), 3.61-3.72 (m, 2H), 4.05 4.12 (m, 2H), 4.32-4.37 (m, 2H), 4.62 (ABq, J = 12.3 Hz, A6 = 0.16, 2H), 5.09 (d, J = 4.0 Hz, 1H), 5.35 (d, J = 5.1 Hz, 1H), 5.33 (d, J = 5.3 Hz, 1H), 5.54-5.58 (m, 1H), 5.56 (s, 1H), 5.82 (d, J = 6.2 Hz, 1H), 7.12-7.18 (m, 1H), 7.18-7.26 (mi, 5H), 7.34 30 7.40 (m, 3H), 7.42-7.46 (mi, 3H), 7.65 (s, 1H), 9.51 (s, 1H); IR (KBr) 3560, 3390, 3260, 3080, 2900, 2880, 1745, 1660, 1590, 1540, 1450, 1425, 1370, 1320, 1280, 1200, 1180, 1140, 1070, 1050, 1025, 970, 755, and 695 cm'; mass spectrum [(+) WO 00/31096 PCT/US99/27828 - 64 FAB], m/z 744 (M + H)', 766 (M + Na)*; Anal. Calcd. for C 3 7

H

4 2C1NO 1 3 : C, 59.72; H, 5.69; N, 1.88, Found: C, 59.75; H, 5.75; N, 2.03. Example 49 5 N- { 5-[(4',6'-O-Benzylidene-6-O-phenvl-propyl-carboxvl- -D-maltosvyl)-oxv methyll-2-chloro-phenvl } -acetamide The title compound was prepared as a white solid (0.210 g, 68%) from N-{5 [(4',6'-O-benzylidene-fp-D-maltosyloxy)-methyl]-2-chloro-phenyl}-acetamide using 4-phenylbutyryl chloride (prepared from 4-phenylbutyric acid and oxalyl chloride) 10 and a procedure similar to Example 2, mp 184-185 oC; 1 H NMR (DMSO-d) 8 1.77 1.86 (m, 2H), 2.07 (s, 3H), 2.34 (t, J = 7.2 Hz, 2H), 2.58 (t, J = 7.5 Hz, 2H), 3.08 3.16 (m, 1H), 3.29-3.51 (m, 4H), 3.53-3.73 (m, 4H), 4.07-4.14 (m, 2H), 4.33-4.38 (m, 2H), 4.62 (ABq, J = 12.3 Hz, A6 = 0.16, 2H), 5.09 (d, J = 4.0 Hz, 1H), 5.28-5.37 (bs, 2H), 5.56 (s, 2H), 5.82 (d, J = 5.3 Hz, 1H), 7.13-7.19 (m, 4H), 7.21-7.27 (m, 15 2H), 7.33-7.37 (m, 3H), 7.40-7.46 (m, 3H), 7.63 (s, 1H), 9.51 (s, 1H); IR (KBr) 3560, 3390, 3260, 3080, 2930, 2900, 2880, 1745, 1665, 1590, 1540, 1450, 1420, 1370, 1320, 1275, 1175, 1140, 1070, 1050, 1025, and 690 cm-'; mass spectrum [(+) FAB], m/z 780/782 (M + Na)*; Anal. Calcd. for C 3 8

H

4 4 C1NO 13 : C, 60.20; H, 5.85; N, 1.85, Found: C, 60.13; H, 5.73; N, 1.99. 20 Example 50 Diphenyl-acetic acid 6-(3-acetylamino-4-chloro-benzvyloxy)-3-(7.8-dihydroxv-2 phenvl-hexahydro-pyranof3.2-d][ 1,31 dioxin-6-vloxy)-4.5-dihydroxy-tetrahydro pyran-2-vlmethyl ester 25 The title compound was prepared as a white foam (0.510 g, 77%) from N-{5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using diphenylacetyl chloride and a procedure similar to Example 2, mp >106 oC (decomp.); 'H NMR (DMSO-d) 8 2.08 (s, 3H), 3.03-3.09 (m, 1H), 3.26-3.38 (m, 3H), 3.41-3.47 (m, 1H), 3.51-3.62 (m, 3H), 3.66-3.73 (m, 1H), 4.02-4.07 (m, 1H), 30 4.15 (q, J = 6.2 Hz, 1H), 4.27 (d, J = 7.7 Hz, 1H), 4.46 (ABq, J = 12.5 Hz, A8 = 0.15, 2H), 4.50 (d, J = 10.8 Hz, 1H), 4.90 (d, J = 4.0 Hz, 1H), 5.27 (s, 1H), 5.31 (d, J = 5.3 Hz, 1H), 5.35 (d, J = 5.3 Hz, 1H), 5.54-5.56 (m, 2H), 5.81 (d, J = 6.4 Hz, 1H), 7.14 WO 00/31096 PCT/US99/27828 - 65 (dd, J = 1.8, 8.3 Hz, 1H), 7.19-7.25 (m, 2H), 7.25-7.34 (m, 8H), 7.34-7.38 (m, 3H), 7.40-7.45 (m, 3H), 7.61 (s, 1H), 9.52 (s, 1H); IR (KBr) 3400, 3050, 2900, 2860, 1730, 1680, 1600, 1530, 1500, 1450, 1420, 1375, 1310, 1275, 1240, 1150, 1070, 1025, 750, and 690 cm

"

'; mass spectrum [(+) FAB], m/z 806/808 (M + H), 828/830 5 (M + Na)*, 844/846 (M + K)+; Anal. Calcd. for C 42

H

44 C1N0 1 3 . 1.0 H 2 0: C, 61.20; H, 5.63; N, 1.70, Found: C, 61.17; H, 5.48; N, 1.59. Example 51 Diphenvl-acetic acid 4.5-diacetoxv-6-(3-acetv1amino-4-chloro-benzvloxy)-3-(7.8 10 diacetoxy-2-phenyl-hexahydro-pyrano[3.2-dI[r 1,3] dioxin-6-vyloxy)-tetrahydro-pyran 2-v1methyl ester The title compound was prepared as a white foam (0.289 g, 76%) from diphenyl-acetic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro 15 pyran-2-ylmethyl ester using a procedure similar to Example 25, mp >99 oC (decomp.); 'H NMR (DMSO-d) 8 1.92 (s, 3H), 1.94 (s, 3H), 1.96 (s, 3H), 1.99 (s, 3H), 2.08 (s, 3H), 3.66 (t, J =9.9 Hz, 1H), 3.72-3.78 (m, 1H), 3.78 (t, J = 9.0 Hz, 1H), 3.87 (t, J = 9.7 Hz, 1H), 3.98-4.05 (m, 2H), 4.18-4.24 (m, 1H), 4.44 (ABq, J = 12.7 Hz, A6 = 0.16, 2H), 4.61-4.67 (m, 2H), 4.80 (d, J = 7.9 Hz, 1H), 4.88 (dd, J = 4.2, 20 10.3 Hz, 1H), 5.16 (d, J = 4.0 Hz, 1H), 5.22 (t, J = 9.9 Hz, 1H), 5.29 (t, J = 9.2 Hz, 1H), 5.31 (s, 1H), 5.60 (s, 1H), 6.99 (dd, J = 1.5, 8.1 Hz, 1H), 7.20-7.25 (m, 2H), 7.27-7.35 (m, 8H), 7.35 (s, 5H), 7.43 (d, J = 8.1 Hz, 1H), 7.59 (s, 1H), 9.51 (s, 1H); IR (KBr) 3410, 3070, 3025, 2930, 2860, 1755, 1690, 1600, 1525, 1450, 1410, 1375, 1240, 1140, 1055, and 1030 cm'; mass spectrum [(+) FAB], m/z 974 (M + H)+, 996 25 (M + Na)*; Anal. Calcd. for C 50 soH 5 2 C1NO 17 1.25 H 2 0: C, 60.24; H, 5.51; N, 1.40, Found: C, 59.97; H, 5.10; N, 1.37.

WO 00/31096 PCT/US99/27828 - 66 Example 52 (3,4-Dimethoxy-phenvyl)-acetic acid 6-(3-acetylamino-4-chloro-benzvloxy)-3-(7,8 dihydroxy-2-phenvl-hexahydro-pyrano F3,2-d][1,3] dioxin-6-vyloxy)-4,5-dihydroxy tetrahydro-pyran-2-vlmethyl ester 5 The title compound was prepared as a white foam (0.316 g, 49%) from N-{5 [(4',6'-O-benzylidene-p3-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using 3,4-dimethoxyphenylacetyl chloride and a procedure similar to Example 2, mp >116 oC (decomp.); 'H NMR (DMSO-d) a 2.07 (s, 3H), 3.07-3.14 (m, 1H), 3.28-3.50 (m, 6H), 3.52-3.65 (m, 4H), 3.67 (s, 3H), 3.68 (s, 3H), 4.07 (dd, J = 4.4, 9.7 Hz, 1H), 10 4.11 (dd, J = 5.5, 12.3 Hz, 1H), 4.31-4.38 (m, 2H), 4.58 (ABq, J = 12.3 Hz, A6 = 0.16, 2H), 4.99 (d, J = 3.7 Hz, 1H), 5.34 (dd, J = 5.3, 9.2 Hz, 2H), 5.55 (s, 1H), 5.57 (d, J = 2.9 Hz, 1H), 5.82 (d, J = 6.2 Hz, 1H), 6.76 (dd, J = 2.0, 8.3 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 6.85 (d, J = 2.0 Hz, 1H), 7.18 (dd, J = 2.0, 8.3 Hz, 1H), 7.34-7.37 (m, 3H), 7.41-7.46 (m, 3H), 7.64 (s, 1H), 9.53 (s, 1H); IR (KBr) 3410, 2920, 1735, 1675, 15 1600, 1520, 1450, 1420, 1375, 1265, 1230, 1140, 1070, and 1025 cm-'; mass spectrum [(+) FAB], m/z 790/792 (M + H)'; Anal. Calcd. for C, 38

H

44 CINOs . 0.5 H20: C, 57.11; H, 5.68; N, 1.75, Found: C, 56.95; H, 5.55; N, 1.71. Example 53 20 (3,4-Dimethoxy-phenvyl)-acetic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro benzyloxy)-3-(7.8-diacetoxy-2-phenyl-hexahydro-pyrano 3,2-dI [ 1,3] dioxin-6-vyloxy) tetrahvdro-pyran-2-vlmethyl ester The title compound was prepared as a white foam (0.105 g, 89%) from (3,4 dimethoxy-phenyl)-acetic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 25 dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy tetrahydro-pyran-2-ylmethyl ester using a procedure similar to Example 25, mp >98 oC (decomp.); 'H NMR (DMSO-d 6 ) 6 1.92 (s, 3H), 1.94 (s, 3H), 1.97 (s, 3H), 1.99 (s, 3H), 2.07 (s, 3H), 3.62-3.77 (m, 4H), 3.66 (s, 3H), 3.67 (s, 3H), 3.89 (t, J = 9.2 Hz, 2H), 3.99-4.03 (m, 1H), 4.10 (dd, J = 10.5, 16.0 Hz, 1H), 4.19 (dd, J = 4.4, 11.9 Hz, 30 1H), 4.44-4.50 (m, 2H), 4.64-4.70 (m, 2H), 4.84 (d, J = 8.1 Hz, 1H), 4.87 (dd, J = 4.0, 10.1 Hz, 1H), 5.21 (d, J = 3.7 Hz, 1H), 5.25 (d, J = 9.9 Hz, 1H), 5.30 (t, J = 9.2 Hz, 1H), 5.62 (s, 1H), 6.77 (dd, J = 1.8, 8.1 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 6.86 WO 00/31096 PCT/US99/27828 - 67 (d, J = 1.8 Hz, 1H), 7.04 (dd, J = 1.8, 8.3 Hz, 1H), 7.35 (s, 5H), 7.44 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 9.51 (s, 1H); IR (KBr) 3370, 2930, 2860, 1755, 1690, 1600, 1520, 1450, 1420, 1370, 1240, 1140, 1055, and 1030 cm'; mass spectrum [(+) FAB], m/z 958/960 (M + H)+, 980/982 (M + Na)'; Anal. Calcd. for C 46

H

5 2 C1NO 1 9 * 1.75 H20: C, 5 55.81; H, 5.65; N, 1.41, Found: C, 55.60; H, 5.14; N, 1.38. Example 54 Nicotinic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7.8-dihydroxy-2-phenvyl hexahydro-pyrano [3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyvran-2 10 v1methyl ester The title compound was prepared as a white solid (0.278 g, 47%) from N-{5 [(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using nicotinoyl chloride hydrochloride and a procedure similar to Example 2, mp >133 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 2.04 (s, 3H), 3.16-3.23 (min, 1H), 3.36 (d, J = 9.4 15 Hz, 1H), 3.36-3.42 (m, 1H), 3.48-3.61 (min, 3H), 3.63 (t, J = 9.4 Hz, 1H), 3.68-3.75 (min, 1H), 3.76-3.80 (min, 1H), 4.04 (dd, J = 4.6, 9.9 Hz, 1H), 4.36-4.41 (min, 2H), 4.64 (d, J = 10.5 Hz, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 5.16 (d, J = 4.0 Hz, 1H), 5.35 (dd, J = 4.0, 5.1 Hz, 2H), 5.52 (s, 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.82 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 1.8, 8.3 Hz, 1H), 7.34-7.38 (min, 3H), 7.39-7.43 (min, 3H), 20 7.57 (ddd, J = 0.7, 4.8, 7.9 Hz, 1H), 7.64 (s, 1H), 8.33 (dt, J = 2.0, 7.9 Hz, 1H), 8.82 (dd, J = 1.8, 4.8 Hz, 1H), 9.12 (d, J = 2.2 Hz, 1H), 9.49 (s, 1H); IR (KBr) 3410, 2910, 2870, 1730, 1625, 1600, 1530, 1455, 1425, 1380, 1290, 1130, 1110, 1070, 1025, 740, and 690 cm'; mass spectrum [(+) FAB], m/z 717/719 (M + H)'; Anal. Calcd. for

C

34

H

3 7 C1N 2 0, 3 . 1.0 H 2 0: C, 55.55; H, 5.35; N, 3.81, Found: C, 55.55; H, 5.30; N, 25 3.78. Example 55 Nicotinic acid 4.5-diacetoxy-6-(3-acetylamino-4-chloro-benzv1oxy)-3-(7,8-diacetoxy 2-phenvl-hexahvdro-pyrano [3,.2-d] [1,3] dioxin-6-vloxy)-tetrahydro-pyran-2-1lmethyl 30 ester The title compound was prepared as a white foam (0.157 g, 73%) from nicotinic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy-2-phenyl- WO 00/31096 PCT/US99/27828 - 68 hexahydro-pyrano[3,2-d] [1,3]dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2 ylmethyl ester using a procedure similar to Example 25, mp >112 oC (decomp.); 'H NMR (DMSO-d) 8 1.94 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.05 (s, 3H), 3.64 (t, J = 9.4 Hz, 1H), 3.69-3.76 (m, 1H), 3.79 (dd, J = 4.2, 9.2 Hz, 1H), 3.87 (t, J = 5 9.4 Hz, 1H), 4.13-4.19 (m, 1H), 4.26 (t, J = 9.4 Hz, 1H), 4.48 (dd, J = 4.0, 12.3 Hz, 1H), 4.64 (ABq, J = 12.7 Hz, A6 = 0.14, 2H), 4.71-4.76 (m, 1H), 4.82 (dd, J = 8.1, 9.2 Hz, 1H), 4.87-4.92 (m, 2H), 5.26 (t, J = 10.1 Hz, 1H), 5.32-5.38 (m, 2H), 5.55 (s, 1H), 7.04 (dd, J = 1.8, 8.1 Hz, 1H), 7.29-7.36 (m, 5H), 7.42 (d, J = 8.1 Hz, 1H), 7.58 (dd, J = 4.8, 8.1 Hz, 1H), 7.61 (s, 1H), 8.39 (dt, J = 2.0, 7.9 Hz, 1H), 8.84 (dd, J = 10 1.5, 4.6 Hz, 1H), 9.17-9.19 (mn, 1H), 9.49 (s, 1H); IR (KBr) 3410, 2940, 2860, 1755, 1690, 1600, 1530, 1450, 1420, 1380, 1290, 1240, 1140, 1055, 1030, and 995 cm'; mass spectrum [(+) FAB], m/z 885 (M + H)+, 907 (M + Na)+; Anal. Calcd. for

C

4 2

H

45 C1N 2 0 1 7 1.0 HO: C, 55.85; H, 5.24; N, 3.10, Found: C, 55.61; H, 4.89; N, 2.99. 15 Example 56 (R)-N-[5-[[[6- O-(4-Benzoylbenzovl)-4- O-[4,6- O-(phenvl1methylene)-a-D 2lucopvranosvyl]--D-glucopyranosvll oxvylmethyll-2-chlorophenv1lacetamide The title compound was prepared as a white powder (0.347 g, 52%) from N 20 { 5-[(4',6'-O-benzylidene-p-D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide using p-benzoylbenzoyl chloride (prepared from p-benzoylbenzoic acid and oxalyl chloride) and a procedure similar to Example 2, mp >117 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 2.03 (s, 3H), 3.17-3.23 (m, 1H), 3.27-3.43 (m, 2H), 3.49-3.66 (mn, 4H), 3.70-3.82 (mn, 2H), 4.08 (4.8, 10.1 Hz, 1H), 4.39-4.44 (m, 2H), 4.64 (d, J = 10.5 Hz, 25 1H), 4.66 (ABq, J = 12.3 Hz, A6 = 0.14, 2H), 5.16 (d, J = 4.0 Hz, 1H), 5.36 (t, J = 5.3 Hz, 2H), 5.53 (s, 1H), 5.60 (d, J = 2.9 Hz, 1H), 5.83 (d, J = 6.2 Hz, 1H), 7.20 (dd, J = 1.8, 8.1 Hz, 1H), 7.33-7.37 (m, 3H), 7.39-7.43 (m, 3H), 7.54-7.59 (m, 2H), 7.65 (s, 1H), 7.67-7.73 (m, 1H), 7.73-7.77 (m, 2H), 7.82-7.86 (m, 2H), 8.13-8.17 (m, 2H), 9.49 (s, 1H); IR (KBr) 3410, 3080, 2910, 2850, 1725, 1660, 1600, 1530, 1450, 1420, 30 1400, 1365, 1270, 1140, 1070, and 1025 cm'; mass spectrum [(-) ESI], m/z 818.1 (M - H); Anal. Calcd. for C 4 2H 42

CINO

4 . 0.5 HO 2 0: C, 60.83; H, 5.23; N, 1.69, Found: C, 60.71; H, 5.28; N, 1.61.

WO 00/31096 PCT/US99/27828 - 69 Example 57 N-f 5-[(4' ,6'-O-Benzvlidene-p-D-maltosvl)-oxy-methyll-2-methyl-phenvl I-acetamide step 1 5 5-[(Hepta-O-acetyl- -D-maltosyl)-oxy-methyl]-2-methyl- 1-nitrobenzene The title compound was prepared as a colorless solid (8.02 g, 53%) from 4 methyl-3-nitrobenzyl alcohol and acetobromomaltose using a procedure similar to step 1 of Example 1, mp 68-74 oC; 'H NMR (DMSO-d) a 1.93 (s, 3 H), 1.94 (s, 3 H), 1.95 (s, 3 H), 1.96 (s, 3 H), 1.97 (s, 3 H), 2.012 (s, 3 H), 2.07 (s, 3 H), 3.93 - 4.01 10 (m, 4 H), 4.13 - 4.21 (m, 2 H), 4.37 (d, 2 H), 4.64 - 4.90 (m, 5 H), 4.97 (t, 1 H), 5.20 (dd, 1 H), 5.27 - 5.33 (m, 2 H), 7.48 (d, 1 H), 7.52 (d, 1H), 7.88 (s, 1 H). IR (KBr) 2950, 1750, 1230 and 1050 cm', mass spectrum [(+FAB)], m/z 808 (M + H)'. Anal. Calcd. for C34H43NO2: C, 51.98; H,5.52; N, 1.78. Found: C, 51.59; H, 5.45; N, 1.86. 15 step 2 5-(Hepta-O-acetyl-0-D-maltosyloxymethyl)-2-methylphenylamine The title compound was prepared as a white foam (5.39 g, 79%) from 5 (hepta-O-acetyl-p-D-maltosyloxymethyl)-2-methyl-l1-nitrobenzene using a procedure similar to step 2 of Example 1; 'H NMR (DMSO-d) 8 1.93 (s, 3 H), 1.94 (s, 3 H), 20 1.95 (s, 3 H), 1.97 (s, 3 H), 1.98 (s, 3 H), 2.03 (s. 6 H), 2.10 (s, 3 H), 3.93 - 4.03 (m, 4 H), 4.14 - 4.23 (m, 2 H), 4.32 - 4.41 (m, 2 H), 4.58 (d, 1 H), 4.68 (t, 1 H), 4.76 4.88 (m, 4 H), 4.98 (t, 1 H), 5.22 (t, 1 H), 5.28 -5.31 (mn, 2 H), 6.37 (d, 2 H), 6.49 (s, 1 H), 6.87 (d, 1 H). 25 step 3 N-[5-(Hepta-O-acetyl- p-D-maltosyloxymethyl)-2-methylphenyl]acetamide The title compound was prepared as a white foam (6.60 g, 91%) from 5 (hepta-O-acetyl-p-D-maltosyloxymethyl)-2-methylphenylamine using a procedure similar to step 3 of Example 1; 'H NMR (DMSO-d) 8 1.93 (s, 3 H), 1.94 (s, 3 H), 30 1.95 (s, 3 H), 1.979 (s, 3 H), 1.984 (s, 3 H), 2.03 (s, 3 H), 2.10 (s, 3 H), 2.18 (s, 3 H), 3.94 - 4.02 (m, 4 H), 4.14 - 4.24 (m, 2 H), 4.40 (d, 1 H), 4.48 (d, 1 H), 4.67 - 4.74 (m WO 00/31096 PCT/US99/27828 - 70 2 H), 4.81 - 4.89 (m 2 H), 4.98 (t, 1 H), 5.19 - 5.32 (m, 3 H), 6.98 (d, 1 H), 7.17 (d, 1 H), 7.33 (s, 1 H), 9.27 (s, 1 H). step 4 5 N-[5-(1-D-Maltosyloxy-methyl)-2-methyl-phenyl]-acetamide A solution containing N-[5-(hepta-O-acetyl-p-D-maltosyloxymethyl)-2 methylphenyl]acetamide (6.60 g, 8.27 mmol) and 25 weight% NaOMe in MeOH (0.893 g, 4.14 mmol) in MeOH (198 mL) was refluxed for 2.5h. The reaction was cooled to room temperature and concentrated to give 4.09 g (98%) of the product as a 10 white foam. This material was used without any additional purification. An analytical sample was obtained by reverse phase HPLC (C18, 15%

CH

3

CN/H

2 0) to give a white solid, mp 115 oC; 1 H NMR (DMSO-d) 6 2.03 (s, 3 H), 2.16 (s, 3 H), 3.04 - 3.09 (m, 2 H), 3.21 - 3.56 (m, 7 H), 3.57 - 3.62 (m, 2 H), 3.70 3.73 (m, 1 H), 4.26 (d, 1 H), 4.48 - 4.54 (m, 3 H), 4.76 (d, 1 H), 4.86 - 4.89 (m, 2 H), 15 5.01 (d, 1 H), 5.17 (d, 1 H), 5.42 (d, 1 H), 5.49 (d, 1 H), 7.10 (d, 1H), 7.15 (d, 1 H), 7.35 (s, 1 H), 9.28 (s, 1 H). IR (KBr) 3375, 2900, 1670 and 1025 cmI', mass spectrum [(+) FAB], m/z 504 (M + H)+, 526 (M + Na)*. Anal. Calcd. for C 22 H 3 3 NO 2 0.5 H20: C, 51.56; H, 6.67; N, 2.73. Found: C, 51.78; H, 6.81; N, 2.75. 20 step 5 N-{5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-methyl-phenyl} acetamide A solution containing N- { 5-[(p-D-maltosyl)-oxy-methyl]-2-methyl-phenyl

}

acetamide (1.88 g, 3.83 mmol), benzaldehyde dimethyl acetal (0.807 mL, 5.36 mmol) 25 and p-toluenesulfonic acid monohydrate (72.7 mg, 0.383 mmol) was heated at 60 oC. After 4h, additional benzaldehyde dimethyl acetal (0.403 mL, 2.68 mmol) and p toluenesulfonic acid monohydrate (36.4 mg, 0.192 mmol) was added and the reaction was heated at 60 oC for 16 h. To the reaction was added K 2

CO

3 and heating was continued for 0.5h. The hot solution was filtered and the filtrate concentrated. 30 Purification by reverse phase HPLC (C18, 15% CH 3

CN:HO

2 0) gave 1.26 g (56%) of the title compound as a white solid, mp 190-197 oC; 'H NMR (DMSO-d) 6 2.04 (s, 3H), 2.16 (s, 3H), 3.08 (t, 1H), 3.35-3.40 (m, 3H), 3.45 (t, 1H), 3.53-3.59 (m, 2H), WO 00/31096 PCT/US99/27828 -71 3.64-3.75 (m, 3H), 4.11 (dd, J = 5.1, 2.4 Hz, 1H), 4.28 (d, 1H), 4.50 (d,1H), 4.67 (t, 1H), 4.77 (d, 1H), 5.13 (d, 1H), 5.21 (br. s, 1H), 5.29 (br. s, 1H), 5.49 (br. s, 1H), 5.57 (s, 1H), 5.61 (br. s, 1H), 7.10 (d, 1H), 7.16 (d, 1H), 7.34-7.38 (m, 4H), 7.42 7.45 (s, 2H), 9.28 (s, 1H); IR (KBr) 3400, 2900, 1650 andl075 cm- 1 ; mass spectrum 5 [(+) ESI], m/z 609 (M + NH 4 )', 614 (M + Na)*; Anal. Calcd. for C29H37NO12 ' 0.5 1-20: C, 57.99; H, 6.30; N, 2.37, Found: C, 57.80; H, 6.39; N, 2.50. Found: C, 57.85; H, 6.33; N, 2.27. Example 58 10 N-Acetyl- { 5-[(2,2',3,3',6-penta-O-acetvl-4',6'-O-benzylidene-p-D-maltosvyl)-oxy methyll-2-methyl-phenvl acetamide At 0 oC, to a stirred solution containing N-{5-[(4',6'-O-benzylidene-3-D maltosyl)-oxy-methyl]-2-methyl-phenyl}-acetamide (0.406 g, 0.686 mmol), pyridine (1.66 mL, 20.6 mmol) and 4-dimethylaminopyridine (0.768 g, 6.86 mmol) was added 15 dropwise acetic anhydride (1.28 mL, 13.7 mmol). After 6h, with reaction eventually warmed to room temperature, the solution was diluted with diethyl ether (100 mL), washed successively with H 2 0 (2x), sat. aq. NaHCO 3 (2x), sat. aq. CuSO (2x), brine (2x), dried (Na 2

SO

4 ) and concentrated. Purification by flash chromatography (3, 4 and 5% MeOH:CHC13 gradient) gave 0.194 g, (34%), of a white solid after cryatallization 20 from CH 2 Cl 2 :petroleum ether, mp 97 oC; 'H NMR (DMSO-d 6 ) 8 1.90 (s, 3H), 1.92 (s, 3H), 1.98 (s, 3H), 1.99 (s, 3H), 2.06 (s, 3H), 2.08 (s, 3H), 2.13 (s, 3H), 2.17 (s, 3H), 3.71-3.80 (m, 2H), 3.95-4.02 (m, 2H), 4.12-4.18 (m, 2H), 4.39 (dd, J = 9.9, 2.2 Hz, 1H), 4.56 (d, 1H), 4.67-4.75 (m, 2H), 4.86-4.90 (m, 2H), 5.22-5,33 (m, 3H), 5.61 (s, 1H), 7.11 (s, 1H), 7.24 (d, 1H), 7.34 (d, 1H), 7.36 (s, 5H); IR (KBr) 3450, 2900, 25 1750 and 1240 cm'; mass spectrum [(+) FAB], m/z 844 (M + H)*, 866 (M + Na)+; Anal. Calcd. for C 4

,H

49 NO,,: C, 58.36; H, 5.85; N, 1.66, Found: C, 57.99; H, 5.76; N, 1.67.

WO 00/31096 PCT/US99/27828 - 72 Example 59 N-(5- { [4',6'-O-Benzylidene-6-O-(4-toluenesulfonvl)--D-maltosVl]-oxy-methyl 1-2 methyl-phenyl)-acetamide At 0 oC, to a stirred solution of N-{5-[(4',6'-O-benzylidene-p-D-maltosyl) 5 oxy-methyl]-2-methyl-phenyl}-acetamide (0.711 g, 1.20 mmol) in pyridine (2.4 mL) was added a solution of p-toluenesulfonyl chloride (0.275 g, 1.44 mmol) in CH 2 C1 2 (1.5 mL). After 2 h, additional p-toluenesulfonyl chloride (0.275 g, 1.44 mmol) in

CH

2 C1 2 (1.5 mL) was added and the solution was stirred at 0 oC for 2h. The reaction was quenched with ice cold HO 2 0 (50 mL) and extracted with EtOAc. The combined 10 organic extracts were washed successively with sat. aq. NaHCO 3 (2x), sat. aq. CuSO 4 (2x), brine (2x), dried (Na 2

SO

4 ) and concentrated. Purification by reverse phase HPLC (C18, 50% CH 3 CN:-H20) gave 0.421 g, (47%) of a colorless solid, mp 115-121 oC; 'H NMR (DMSO-d) a 2.05 (s, 3H), 2.17 (s, 3H), 2.33 (s, 3H), 3.05 (t, 1H), 3.24 3.44 (m, 4H), 3.52 (t, 1H), 3.58-3.62 (m, 3H), 3.95 (d, 1H), 4.13 (dd, 1H), 4.28 (d, 15 1H), 4.33 (d, 1H), 4.41 (d, 1H14), 4.59 (d, 1H), 5.05 (d, 1H1), 5.57 (s, 1H), 7.06 (d, 1H), 7.16 (d, 1H), 7.33-7.47 (m, 8H), 7.78 (d, 2H), 9.29 (s, 1H); IR (KBr) 3375, 2900, 1650, 1350, 1175 and 1075 cm"; mass spectrum [(+) FAB], m/z 746 (M + H)', 768 (M + Na)*; Anal. Calcd. for C 36

H

43 NO4S H20: C, 56.61; H, 5.94; N, 1.83, Found: C, 56.61; H, 5.77; N, 1.80. 20 Example 60 N- { 5-[(4',6'-O-Benzvlidene-6- O-phenvl--D-maltosvl)-oxy-methyll-2-chloro phenyl -acetamide At ambient temperature, to a stirred solution of phenol (0.0784 g, 0.833 25 mmol) in DMF (10 mL) was added potassium-t-butoxide (0.0982 g, 0.833 mmol). After 0.5 h, to the reaction was added a solution of N-(5-{[2,3,2',3'-tetra-O-acetyl 4' ,6'-O-benzylidene-6-O-(4-toluenesulfonyl)-p3-D-maltosyl]-oxy-methyl }-2-chloro phenyl)-acetamide (0.389 g, 0.417 mmol) in DMF (4 mL) and the reaction was heated at 65 'C for 3 h. The reaction was cooled to ambient temperature, quenched 30 with H20 (40 mL), extracted with EtOAc, dried (Na 2

SO

4 ) and concentrated. The crude product was dissolved in MeOH (10 mL) and treated with 25 weight% NaOMe in MeOH (45 mg) at 65 oC for 3 h. The reaction was cooled to ambient temperature WO 00/31096 PCT/US99/27828 - 73 and concentrated. Purification by flash chromatography (5 and 10% MeOH:CHC13 gradient) gave 0.149 g (39%) of title compound as a solid; 'H NMR (DMSO-d) 8 2.05 (s, 3H), 3.13-3.19 (m, 1H), 3.27-3.40 (m, 2H), 3.44-3.66 (m, 5H), 3.70-3.73 (m, 2H), 4.14 (dd, J = 10.8, 4.4 Hz, 1H), 4.23 (d, J = 10.9 Hz, 1H), 4.39 (d, J = 7.7 5 Hz, 1H), 4.64 (ABq, J = 12.3 Hz, A6 = 0.08, 2H), 5.16 (d, J = 3.7 Hz, 1H), 5.28 (d, J = 5.1 Hz, 1H), 5.33 (d, J = 5.3 Hz, 1H), 5.47 (s, 1H), 5.56 (d, J = 3.3 Hz, 1H), 5.67 (d, J = 6.4 Hz, 1H), 6.90-6.97 (m, 3H), 7.20 (dd, J = 8.2, 1.9 Hz, 1H), 7.25-7.29 (m, 2H), 7.32-7.36 (m, 5H), 7.42 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 9.50 (s, 1H); IR (KBr) 3400, 2900, 1650 and 1070 cm'; mass spectrum [(+) FAB], m/z 710 (M + Na)*; Anal. 10 Calcd. for C34H3,NC1002: C, 59.34; H, 5.57; N, 2.03, Found: C, 58.96; H, 5.78; N, 2.16. Example 61 (R)-N-[ 2-Chloro-5-[[[4-O-[4',6'-O-(phenvylmethylene)-a-D- glucopvranosv11y-3-D 15 2lucopvranosvll oxv]methyll phenvyl]-3-pyridinecarboxamide step 1 N-[2-Chloro-5-[[[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a.-D glucopyranoysl)- -D-glucopyranosyl]oxy]methyl]phenyl]-3-pyridinecarboxanmide To a stirred solution of 2-chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl) 20 phenylamine (0.200 g, 0.258 mmol) and triethylamine (0.119 mL, 0.851 mmol) in THF (3 mL) at 0 oC was added nicotinoyl chloride hydrochloride (0.0551 mg, 0.310 mmol). After 0.5 h at this temperature, it was warmed to rt and stirred an additional 18 h. At this point, the solid was filtered off and washed with additional THF (10 mL). The filtrate was then concentrated and taken up in EtOAc (100 mL). This 25 organic solution was washed with 1H20 (10 mL) and brine (10 mL) and then dried (Na 2 SO4). After concentration, the residue was purified by preparatory plate chromatography (10:90 MeOH:CHC,13) to afford the product (0.183 g, 80%) as a white foam, mp 83-86 oC; 'H NMR (CDC13) 5 1.99 (s, 3H), 2.00 (s, 3H), 2.02 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H), 2.10 (s, 3H), 2.16 (s, 3H), 3.67-3.72 (m, 1H), 3.93-3.98 30 (m, 1H), 4.04 (dd, J = 2.2, 11.9 Hz, 2H), 4.25 (dt, J = 3.7, 12.5 Hz, 2H), 4.53 (dd, J = 2.9, 12.3 Hz, 1H), 4.60 (d, J = 7.7 Hz, 1H), 4.64 (d, J = 12.5 Hz, 1H), 4.83-4.93 (m, 3H), 5.05 (t, J = 10.1 Hz, 1H), 5.23 (t, J = 9.4 Hz, 1H), 5.34 (dd, J = 9.7, 10.5 Hz, WO 00/31096 PCT/US99/27828 - 74 1H), 5.41 (d, J = 4.2 Hz, 1H), 7.07 (dd, J = 2.0 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.48 (ddd, J = 0.9, 4.8, 7.9 Hz, 1H), 8.23 (ddd, J = 1.5, 2.2, 7.9 Hz, 1H), 8.43 (s, 1H), 8.48 (d, J = 2.0 Hz, 1H), 8.82 (dd, J = 1.5, 4.8 Hz, 1H), 9.15 (dd, J = 0.7, 2.2 Hz, 1H); IR (KBr) 3400, 2950, 1755, 1675, 1600, 1550, 1420, 1375, 1235, and 1050 cm'; 5 mass spectrum [(+) FAB], m/z 881 (M + H)+, 903 (M + Na)'; Anal. Calcd. for

C

3 9

H

45 C1N 2 019 2.0 H20: C, 51.07; H, 5.38; N, 3.05, Found: C, 50.80; H, 4.83; N, 2.89. step 2 10 N-[2-chloro-5-[[(4-O-a-D-glucopyranosyl-p-D-glucopyranosyl)oxy]methyl] phenyl]-3-pyridinecarboxamide The title compound was prepared as a white foam (1.97 g, 57%) from N-[2 chloro-5-[[[2,3,6-tri- O-acetyl-4- O-( 2

,

3

,

4

,

6 -tetra-O-acetyl-a-D-glucopyranoysl)-p-D glucopyranosyl]oxy]methyl]phenyl]-3-pyridinecarboxamide using a procedure 15 similar to step 4 of Example 1, mp >106 oC (decomp.); 1 H NMR (DMSO-d) 8 3.02 3.13 (m, 2H), 3.19-3.29 (m, 2H), 3.31-3.39 (m, 1H), 3.39-3.50 (m, 3H), 3.55-3.63 (m, 2H), 3.70-3.76 (m, 1H), 4.09 (q, J = 5.3 Hz, 1H), 4.31 (d, J = 7.9 Hz, 1H), 4.49 4.55 (m, 2H), 4.60 (d, J = 12.5 Hz, 1H), 4.84-4.91 (m, 3H), 5.01 (d, J = 3.7 Hz, 1H), 5.26 (d, J = 5.1 Hz, 1H), 5.43 (d, J = 6.4 Hz, 1H), 5.52 (d, J = 3.1 Hz, 1H), 7.35 (dd, 20 J = 2.0, 8.3 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.56-7.60 (m, 2H), 8.31 (dt, J = 2.0, 7.9 Hz, 1H), 8.77 (dd, J = 1.5, 4.8 Hz, 1H), 9.12-9.14 (m, 1H), 10.34 (s, 1H); IR (KBr) 3390, 2910, 2320, 1660, 1590, 1525, 1475, 1450, 1420, 1360, 1310, 1190, 1140, 1080, and 1030 cm'; mass spectrum [(+) FAB], m/z 587 (M + H)+, 609 (M + Na)*, Anal. Calcd. for C 25

H

31 C1N 2 0,, 1 . 1.5 H20: C, 48.90; H, 5.58; N, 4.56, Found: 25 C, 49.18; H, 5.52; N, 4.32. step 3

(R)-N-[

2 -Chloro-5-[[[ 4 -O-[4',6'-O-(phenylmethylene)-a-D-glucopyranosyl] -p-D glucopyranosyl]oxy]methyl] phenyl]-3-pyridinecarboxamide 30 The title compound was prepared as a white solid (1.25 g, 57%) from N-[2 chloro-5-[[(4-O-a-D-glucopyranosyl-p-D-glucopyranosyl)oxy]methyl] phenyl]-3 pyridinecarboxamide using a procedure similar to Example 24, mp 208-210 oC; 'H WO 00/31096 PCT/US99/27828 - 75 NMR (DMSO-d) a 3.08-3.15 (m, 1H), 3.30-3.42 (m, 4H), 3.42-3.51 (m, 1H), 3.51 3.60 (m, 2H), 3.64-3.76 (m, 3H), 4.12 (dd, J = 3.3, 8.6 Hz, 1H), 4.33 (d, J = 7.7 Hz, 1H), 4.68 (t, J = 5.7 Hz, 1H), 4.74 (ABq, J = 12.5 Hz, AS = 0.22, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.30 (t, J = 4.4 Hz, 2H), 5.52 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.63 (d, J = 5 6.6 Hz, 1H), 7.34-7.38 (m, 4H), 7.42-7.46 (m, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.55 7.60 (m, 2H), 8.31 (dt, J = 1.8, 7.9 Hz, 1H), 8.77 (dd, J = 1.8, 4.8 Hz, 1H), 9.13 (dd, J = 0.7, 2.2 Hz, 1H), 10.34 (s, 1H); IR (KBr) 3530, 3400, 2920, 2830, 1680, 1590, 1540, 1460, 1420, 1380, 1320, 1275, 1150, 1120, 1070, and 1025 cm'; mass spectrum [(+) FAB], m/z 675/677 (M + H)', 697/699 (M + Na)*; Anal. Calcd. for 10 C 32

H

3 5

CIN

2 0 1 2 0.5 H 2 0: C, 56.18; H, 5.30; N, 4.09, Found: C, 56.31; H, 5.13; N, 4.19. Example 62 (R)-N-[5-[[[6-O-Benzovl-4-O-[4',6'-O-(phenvylmethylene)-a-D- lucopvranosyll-3-D 15 glucopyranosylloxylmethyl]l-2-chlorophenvyl-3-pyridinecarboxamide The title compound was prepared as a off-white glassy solid (0.628 g, 44%) from (R)-N-[2-chloro-5-[[[4-O-[4,6-O-(phenylmethylene)-c-D-glucopyranosyl]-3-D glucopyranosyl]oxy]methyl] phenyl]-3-pyridinecarboxamide using a procedure similar to Example 2, mp 190-193 oC; 'H NMR (DMSO-d) 6 3.17-3.24 (m, 1H), 20 3.30-3.43 (m, 2H), 3.50-3.64 (m, 4H), 3.68-3.76 (m, 1H), 3.78 (ddd, J = 1.5, 5.1, 9.7 Hz, 1H), 4.50 (dd, J = 4.8, 9.9 Hz, 1H), 4.36 (dd, J = 5.1, 12.1 Hz, 1H), 4.43 (d, J = 7.7 Hz, 1H), 4.59-4.64 (m, 1H), 4.71 (ABq, J = 12.7 Hz, AS = 0.14, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.35 (d, J = 5.1 Hz, 1H), 5.39 (d, J = 5.3 Hz, 1H), 5.52 (s, 1H), 5.59 (d, J = 3.1 Hz, 1H), 5.80 (d, J = 6.4 Hz, 1H), 7.31-7.37 (m, 4H), 7.39-7.43 (m, 2H), 7.51 25 (dd, J = 5.9, 7.9 Hz, 3H), 7.54-7.58 (m, 2H), 7.60-7.66 (m, 1H), 7.98 (dd, J = 1.1, 8.1 Hz, 2H), 8.29 (dt, J = 1.8, 7.9 Hz, 1H), 8.77 (dd, J = 1.8, 4.8 Hz, 1H), 9.11 (d, J = 2.0 Hz, 1H), 10.31 (s, 1H); IR (KBr) 3410, 3080, 2900, 2850, 1720, 1680, 1590, 1530, 1440, 1420, 1375, 1320, 1275, 1070, 1025, 755, and 710 cm'; mass spectrum [(+) FAB], m/z 779/781 (M + H)+, 801/803 (M + Na) ; Anal. Calcd. for C 3 9 9

H

9 C1N 2 0 13 30 0.5 HO0: C, 59.43; H, 5.12; N, 3.55, Found: C, 59.34; H, 4.91; N, 3.45.

WO 00/31096 PCT/US99/27828 - 76 Example 63 Furan-2-carboxylic acid { 5- (4',6'-O-benzylidene-f-D-maltosyl)-oxy-methyll-2 chloro-phenylv}-amide step 1 5 Furan-2-carboxylic acid {5-[(2,2',3,3',4',6,6'-hepta-O-acetyl-3-D-maltosyl) oxymethyl]-2-chloro-phenyl}-amide The title compound was prepared as a white foam (1.47 g, 94%) from 2 chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenylamine using a procedure similar to step 3 of Example 1, mp >85 oC (decomp.); 'H NMR (DMSO-d) a 1.93 (s, 10 6H), 1.94 (s, 3H), 1.969 (s, 3H), 1.972 (s, 3H), 2.01 (s, 3H), 2.07 (s, 3H), 3.92-4.02 (m, 4H), 4.12-4.23 (m, 2H), 4.38 (dd, J = 2.2, 12.1 Hz, 1H), 4.67 (ABq, J = 13.0 Hz, A6 = 0.15, 2H), 4.73 (dd, J = 7.9, 9.4 Hz, 1H), 4.83-4.90 (m, 2H), 4.97 (t, J = 9.7 Hz, 1H), 5.21 (t, J = 10.1 Hz, 1H), 5.27 (d, J = 4.2 Hz, 1H), 5.31 (d, J = 9.2 Hz, 1H), 6.70 (q, J = 1.8 Hz, 1H), 7.18 (dd, J = 2.0, 8.3 Hz, 1H), 7.32 (d, J = 3.5 Hz, 1H), 7.53 (d, J 15 = 8.1 Hz, 1H), 7.57 (d, J = 2.0 Hz, 1H), 7.93-7.95 (m, 1H), 9.84 (s, 1H); IR (KBr) 3390, 3130, 2950, 1755, 1690, 1590, 1530, 1445, 1420, 1375, 1320, 1230, 1140, and 1040 cm'; mass spectrum [(+) FAB], m/z 870 (M + H)+, 892 (M + Na)', Anal. Calcd. for C 3 8

H

44 C1NO 20 1.0 H,0: C, 51.39; H, 5.22; N, 1.58, Found: C, 51.00; H, 4.93; N, 1.51. 20 step 2 Furan-2-carboxylic acid {2-chloro-5-[(p3-D-maltosyl)-oxy-methyl]-phenyl}-amide A solution containing furan-2-carboxylic acid {5-[(2,2',3,3',4',6,6'-hepta-O acetyl-p-D-maltosyl)-oxymethyl]-2-chloro-phenyl}-amide (1.36 g, 1.56 mmol) and 25 25 weight % NaOMe in MeOH (26.8 pL, 0.468 mmol) in MeOH (41 ml) was stirred at rt for 18 h. At this point, the mixture was concentrated, and the resulting residue was triturated with Et,O to afford the product (0.890 g, 99%) as a white foam, mp >127 oC (decomp.); 'H NMR (DMSO-d) a 3.01-3.12 (m, 2H), 3.21 (dd, J = 3.7, 9.7 Hz, 1H), 3.24-3.29 (m, 1H), 3.29-3.38 (m, 2H), 3.38-3.50 (m, 3H), 3.54-3.63 (m, 2H), 30 3.73 (d, J = 12.3 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.45-4.58 (m, 2H), 4.71 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 4.83-4.93 (bs, 2H), 5.01 (d, J = 4.0 Hz, 1H), 5.18-5.32 (bs, 1H), 5.34-5.58 (bs, 2H), 6.69 (dd, J = 1.5, 3.3 Hz, 1H), 7.26-7.33 (m, 2H), 7.50 (d, J WO 00/31096 PCT/US99/27828 - 77 = 8.3 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7.92-7.94 (m, 1H), 9.82-9.94 (bs, 1H); IR (KBr) 3400, 2920, 2880, 1675, 1590, 1530, 1445, 1425, 1365, 1315, 1140, 1080, 1030, and 755 cm; mass spectrum [(+) FAB], m/z 598/600 (M + Na)*, Anal. Calcd. for C 2 4

H

30 C1N0 1 3 * 0.5 HO: C, 49.28; H, 5.34; N, 2.39, Found: C, 49.06; H, 5.34; N, 5 2.21. step 3 Furan-2-carboxylic acid {5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-amide 10 The title compound was prepared as a white solid (0.352 g, 63%) from furan 2-carboxylic acid { 2-chloro-5-[(P-D-maltosyl)-oxy-methyl]-phenyl }-amide using a procedure similar to Example 24, mp 224-226 oC; 'H NMR (DMSO-d) a 3.07-3.14 (m, 1H), 3.27-3.42 (m, 4H), 3.42-3.49 (m, 1H), 3.51-3.59 (m, 2H), 3.63-3.76 (m, 3H), 4.11 (dd, J = 2.4, 7.9 Hz, 1H), 4.32 (d, J = 7.7 Hz, 1H), 4.67 (t, J = 5.9 Hz, 1H), 15 4.72 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.29 (t, J = 6.2 Hz, 2H), 5.51 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.62 (d, J = 6.8 Hz, 1H), 6.68-6.72 (M, 1H), 7.30-7.34 (m, 2H), 7.34-7.38 (m, 3H), 7.41-7.46 (m, 2H), 7.52 (d, J = 8.1 Hz, 1H), 7.62 (s, 1H), 7.94 (t, J = 0.9 Hz, 1H), 9.88 (s, 1H); IR (KBr) 3390, 2920, 2850, 1680, 1600, 1590, 1530, 1455, 1430, 1385, 1320, 1280, 1140, 1070, 1050, 1025, and 20 750 cm-'; mass spectrum [(-) FAB], m/z 662 (M - H); Anal. Calcd. for C 31

H

34 CINO 13 1.0 HO: C, 54.59; H, 5.32; N, 2.05, Found: C, 54.82; H, 4.91; N, 2.03. Example 64 Furan-2-carboxylic acid { 5-[(6-O-benzovl-4',6'-O-benzvlidene-p-D-maltosvyl)-oxy 25 methyll-2-chloro-phenvl }-amide The title compound was prepared as a white solid (0.130 g, 47%) from furan 2-carboxylic acid { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-amide using a procedure similar to Example 2, mp >142 oC (decomp.); 'H NMR (DMSO-d) 6 3.16-3.23 (m, 1H), 3.27-3.42 (m, 2H), 3.49-3.64 (m, 4H), 3.71 30 (dd, J = 5.1, 10.1 Hz, 1H), 3.75-3.80 (m, 1H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H), 4.36 (dd, J = 5.3, 12.3 Hz, 1H), 4.42 (d, J = 7.9 Hz, 1H), 4.58-4.63 (m, 2H), 4.78 (d, J = 12.7 Hz, 1H), 5.14 (d, J = 3.7 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.38 (d, J = 5.3 Hz, WO 00/31096 PCT/US99/27828 - 78 1H), 5.52 (s, 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.79 (d, J = 6.2 Hz, 1H), 6.69 (q, J = 1.8 Hz, 1H), 7.26-7.32 (m, 2H), 7.33-7.38 (m, 3H), 7.38-7.44 (m, 2H), 7.47 (d, J = 8.3 Hz, 1H), 7.51 (t, J = 7.9 Hz, 2H), 7.61 (d, J = 2.0 Hz, 1H), 7.61-7.66 (m, 1H), 7.93 (dd, J = 0.7, 2.6 Hz, 1H), 7.99 (dd, J = 5.3, 7.0 Hz, 2H), 9.85 (s, 1H); IR (KBr) 3460, 5 3380, 3140, 3080, 2880, 1730, 1660, 1590, 1535, 1445, 1425, 1375, 1320, 1275, 1140, 1120, 1075, 1025, 980, and 715 cm'; mass spectrum [(+) ESI], m/z 768 (M + H)+, 790 (M + Na)*; Anal. Calcd. for C 3 8

H

3 8 C1NO4 * 1.0 H20: C, 58.05; H, 5.13; N, 1.78, Found: C, 57.96; H, 4.93; N, 1.76. 10 Example 65 N-f 2-Chloro-5-[(4',.6'-O-benzylidene--D-maltosvyl)-oxv-methyll-phenyl } -pent-4 enamide step 1 N-[2-Chloro-5-[[[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D 15 glucopyranosyl)-p-D-gluopyranosyl]oxy]methyl]phenyl]-4-pentenamide To a stirred solution of 4-pentenoic acid (57.9 gL, 0.567 mmol) and DMF (cat. amt.) in CH 2

C

2 (3 mL) at rt was added oxalyl chloride (49.4 ptL, 0.567 mmol) dropwise. After 5 min. at this temperature, it was heated to 40 oC for an additional 10 min. This completed the preparation of the acid chloride starting material. At this 20 point, to a second stirred solution of NaH (0.0206 g, 0.515 mmol) and CH Cl, (3 mL) at rt was added 2-chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenylamine (0.400 mg, 0.515 mmol). After 10 min., the acid chloride solution was added to this solution dropwise. The reaction was stirred at rt for 1 h and then diluted with EtOAc (100 mL). This layer was washed with IN HC1 (10 mL), sat. NaHCO 3 (10 mL), and 25 brine (10 mL) and then dried (MgSO 4 ). After concentration, the oilly residue was purified by flash chromatography (10:90 to 70:30 EtOAc:petroleum ether gradient) to afford the product (0.321 g, 73%) as a white foam, mp >68 oC (decomp.); 'H NMR (DMSO-d) 8 1.93 (s, 3H), 1.94 (s, 6H), 1.969 (s, 3H), 1.972 (s, 3H), 2.01 (s, 3H), 2.08 (s, 3H), 2.29-2.36 (m, 2H), 2.44-2.49 (m, 2H), 3.92-4.02 (m, 4H), 4.13-4.22 (m, 30 2H), 4.38 (d, J = 10.1 Hz, 1H), 4.53 (d, J = 12.7 Hz, 1H), 4.69-4.75 (m, 2H), 4.84 (d, J = 3.7 Hz, 1H), 4.87 (d, J = 2.9 Hz, 1H), 4.94-5.01 (m, 2H), 5.07 (dd, J = 2.0, 17.4 Hz, 1H), 5.21 (t, J = 9.7 Hz, 1H), 5.27 (d, J = 3.7 Hz, 1H), 5.31 (d, J = 8.8 Hz, 1H), WO 00/31096 PCT/US99/27828 - 79 5.80-5.91 (m, 1H), 7.08 (dd, J = 2.0, 8.3 Hz, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.61 (s, 1H), 9.49 (s, 1H); IR (KBr) 3400, 2950, 1755, 1690, 1630, 1590, 1525, 1420, 1370, 1235, and 1050 cm'; mass spectrum [(+) FAB], m/z 858/860 (M + H)+, 880/882 (M + Na)*, Anal. Calcd. for C 38

H

48 C1N0,19*- 0.5 H 2 0: C, 52.63; H, 5.69; N, 1.62, Found: 5 C, 52.65; H, 5.66; N, 1.59. step 2 N-{2-Chloro-5-[(p-D-maltosyl)-oxy-methyl]-phenyl}-pent-4-enylamide The title compound was prepared as an off-white solid (0.0614 g, 93%) from 10 N-[2-chloro-5-[[[2,3,6-tri-O-acetyl-4-0-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl) -D-glucopyranosyl]oxy]methyl]phenyl]-4-pentenamide and a procedure similar to step 4 of Example 1, mp >103 oC (decomp.); 'H NMR (DMSO-d) 6 2.30-2.37 (m, 2H), 2.43-2.49 (m, 2H), 3.02-3.10 (m, 2H), 3.19-3.28 (m, 2H), 3.30-3.49 (m, 5H), 3.54-3.63 (m, 2H), 3.72 (d, J = 10.8 Hz, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.40-4.67 (m, 15 2H), 4.54 (d, J = 12.3 Hz, 1H), 4.72-4.96 (m, 2H), 4.80 (d, J = 12.3 Hz, 1H), 4.96 5.04 (m, 2H), 5.08 (dd, J = 1.5, 17.1 Hz, 1H), 5.13-5.33 (bs, 1H), 5.33-5.59 (bs, 2H), 5.80-5.92 (m, 1H), 7.22 (dd, J = 1.5, 8.1 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.63 (s, 1H), 9.51 (s, 1H); IR (KBr) 3400, 2910, 1665, 1590, 1530, 1440, 1420, 1370, 1310, 1140, 1070, and 1035 cm'; mass spectrum [(+) FAB], m/z 564/566 (M + H)', 20 586/588 (M + Na) , Anal. Calcd. for C24H 3 4 C1NO1 2 : C, 51.11; H, 6.06; N, 2.48, Found: C, 51.17; H, 6.06; N, 2.36. step 3

N-{

2 -Chloro-5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-phenyl}.-pent-.4.

25 enamide The title compound was prepared as a white powder (0.102 g, 88%) from N { 2-chloro-5-[(p-D-maltosyl)-oxy-methyl]-phenyl}-pent-4-enylamide using a procedure similar to Example 24, mp 191-193 oC; 'H NMR (DMSO-d 6 ) 6 2.30-2.37 (m, 2H), 2.43-2.49 (m, 2H), 3.06-3.13 (m, 1H), 3.28-3.33 (m, 1H), 3.34-3.41 (m, 30 3H), 3.43-3.49 (m, 1H), 3.51-3.60 (m, 2H), 3.64-3.75 (m, 3H), 4.11 (dd, J = 2.9, 8.1 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.67 (t, J = 5.9 Hz, 1H), 4.68 (ABq, J = 12.3 Hz, A6 = 0.22, 2H), 4.99 (dd, J = 2.0, 10.3 Hz, 1H), 5.08 (dd, J = 1.8, 17.1 Hz, 1H), 5.14 WO 00/31096 PCT/US99/27828 - 80 (d, J = 3.7 Hz, 1H), 5.25 (d, J = 5.3 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 5.51 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.63 (d, J = 6.6 Hz, 1H), 5.81-5.91 (m, 1H), 7.23 (dd, J = 2.0, 8.3 Hz, 1H), 7.34-7.38 (m, 3H), 7.42-7.47 (m, 3H), 7.64 (d, J = 1.5 Hz, 1H), 9.51 (s, 1H); IR (KBr) 3410, 2900, 2870, 1670, 1640, 1590, 1535, 1445, 1420, 1375, 1370, 5 1325, 1310, 1270, 1150, 1070, and 1030 cm'; mass spectrum [(+) FAB], m/z 652/654 (M + H)

+

, 674/676 (M + Na)*; Anal. Calcd. for C 3 1

H

3 8 C1NO 1 2 : C, 57.10; H, 5.87; N, 2.15, Found: C, 56.76; H, 5.81; N, 2.31. Example 66 10 N-f{ 2-Chloro-5-[ (6-O-benzovl-4',6'-O-benzilidene-p-D-maltosyl)-oxy-methyll phenvyl I -pent-4-enamide The title compound was prepared as a white solid (1.10 g, 84%) from N-{2 chloro-5-[(4' ,6'-O-benzylidene-p3-D-maltosyl)-oxy-methyl]-phenyl}-pent-4-enamide using a procedure similar to Example 2, mp >110 oC (decomp.); 1 H NMR (DMSO 15 d 6 ) 8 2.28-2.35 (m, 2H), 2.41-2.46 (m, 2H), 3.16-3.23 (m, 1H), 3.28-3.43 (m, 2H), 3.48-3.64 (m, 4H), 3.68-3.73 (m, 1H), 3.73-3.79 (m, 1H), 4.03-4.08 (m, 1H), 4.33 4.38 (m, 1H), 4.39 (d, J = 7.7 Hz, 1H), 4.58-4.63 (m, 1H), 4.65 (ABq, J = 12.5 Hz, A6 = 0.14, 2H), 4.95-4.99 (m, 1H), 5.06 (dd, J = 2.0, 17.4 Hz, 1H), 5.13 (d, J = 4.0 Hz, 1H), 5.35 (t, J = 4.8 Hz, 2H), 5.52 (s, 1H), 5.57 (d, J = 2.9 Hz, 1H), 5.80 (d, J = 20 6.4 Hz, 1H), 5.81-5.90 (m, 1H), 7.20 (dd, J = 2.0, 8.1 Hz, 1H), 7.33-7.37 (m, 3H), 7.38-7.43 (m, 3H), 7.50-7.55 (m, 2H), 7.62 (d, J = 1.5 Hz, 1H), 7.63-7.68 (m, 1H), 7.99 (dd, J = 1.1, 8.3 Hz, 2H), 9.49 (s, 1H); IR (KBr) 3400, 3270, 3080, 2910, 2880, 1725, 1660, 1590, 1530, 1445, 1425, 1375, 1325, 1275, 1140, 1070, 1025, 990, and 715 cm'; mass spectrum [(+) FAB], m/z 756/758 (M + H)', 778/780 (M + Na)*; Anal. 25 Calcd. for C 38

H

42 C1N0 3 - 0.5 H 2 0: C, 59.65; H, 5.66; N, 1.83, Found: C, 59.73; H, 5.64; N, 1.75. Example 67 5-(6-O-Benzov1-4'.6'-O-benzylidene--D-maltosvl)-oxy-methyl-2-chloro 30 phenylamine To a stirred solution of N-{2-chloro-5-[(6-O-benzoyl-4',6'-O-benzilidene-p D-maltosyl)-oxy-methyl]-phenyl }-pent-4-enamide (0.681 g, 0.901 mmol) in WO 00/31096 PCT/US99/27828 - 81 THF:H 2 O (1:1, 50 mL) at rt was added iodine (0.685 g, 2.70 mmol). After 5 min. at this temperature, it was quenched with solid Na 2

S

2 0 3 until brown color went clear. The mixture was diluted with EtOAc (100 mL), washed with brine (10 mL), and then dried (Na 2 SO4). After concentration, the oilly residue was purified by flash 5 chromatography (1:99 to 13:87 MeOH:CHC1, gradient) to afford the product (0.483 g, 80%) as a white solid, mp 168-171 oC; 'H NMR (DMSO-d) 8 3.17 (t, J = 8.3 Hz, 1H1), 3.31-3.43 (m, 2H), 3.48-3.63 (m, 4H), 3.68-3.77 (m, 2H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H1), 4.32-4.38 (m, 2H), 4.52 (ABq, J = 11.9 Hz, A6 = 0.18, 2H), 4.61 (d, J = 10.5 Hz, 1H1), 5.14 (d, J = 3.7 Hz, 1H), 5.22-5.32 (bs, 3H), 5.32-5.39 (bs, 1H), 5.52 10 (s, 1H1), 5.57 (s, 1H1), 5.76-5.83 (bs, 1H1), 6.53 (dd, J = 1.8, 8.1 Hz, 1H), 6.75 (d, J = 2.0 Hz, 1H), 7.08 (7.9 Hz, 1H), 7.33-7.37 (m, 3H), 7.38-7.44 (m, 2H), 7.51-7.56 (m, 2H), 7.63-7.68 (m, 1H), 8.00 (dd, J = 0.7, 7.9 Hz, 2H); IR (KBr) 3390, 2920, 2860, 1730, 1620, 1590, 1495, 1440, 1430, 1370, 1315, 1270, 1070, 1025, 1000, and 710 cm'; mass spectrum [(+) FAB], m/z 674/676 (M + H)+, 696/698 (M + Na)*; Anal. 15 Calcd. for C 3 3 H3 6 C1NO, 2 . 1.0 H20: C, 57.27; H, 5.53; N, 2.02, Found: C, 57.28; H, 5.39; N, 1.99. Example 68 (4-Chloro)-benzyl-4',6'-O-benzylidene-B3-D-maltoside 20 step 1 (4-Chloro-benzyl)-2,2',3,3',4',6,6'-hepta-O-acetyl-p-D-maltoside The title compound was prepared as white needles (3.96 g, 73%) from acetobromomaltose using 4-chloro-benzyl alcohol and a procedure similar to step 1 of Example 1, mp 138-141 oC; 'H NMR (DMSO-d) 8 1.994 (s, 3H), 1.999 (s, 3H), 2.00 25 (s, 3H), 2.025 (s, 3H), 2.029 (s, 3H), 2.10 (s, 3H), 2.16 (s, 3H), 3.66 (ddd, J = 2.9, 4.4, 9.9 Hz, 1H), 3.96 (ddd, J = 2.4, 4.0, 10.1 Hz, 1H), 4.00-4.07 (m, 2H), 4.21-4.28 (m, 2H), 4.51 (dd, J = 2.9, 12.3 Hz, 1H), 4.56 (d, J = 2.4 Hz, 1H1), 4.58 (d, J = 6.8 Hz, 1H), 4.80-4.92 (m, 3H11), 5.05 (t, J = 9.9 Hz, 1H1), 5.22 (t, J = 9.2 Hz, 1H), 5.35 (dd, J = 9.4, 10.3 Hz, 1H11), 5.41 (d, J = 4.0 Hz, 1H), 7.21 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 30 8.3 Hz, 2H11); IR (KBr) 3480, 2960, 2880, 1755, 1650, 1610, 1495, 1440, 1375, 1335, 1240, 1170, 1135, 1050, 935, 910, 820, and 615 cm; mass spectrum [(+) FAB], m/z WO 00/31096 PCT/US99/27828 - 82 761/763 (M + H)', 783/785 (M + Na)*, Anal. Calcd. for C 33

H

4 1 C10 8: C, 52.08; H, 5.43; N, 0.00, Found: C, 51.88; H, 5.37; N, 0.01. step 2 5 (4-Chloro-benzyl)-p3-D-maltoside The title compound was prepared as a white foam (1.55 g, 95%) from (4 chloro-benzyl)-2,2',3,3',4',6,6'-hepta-O-acetyl-p-D-maltoside using a procedure similar to step 4 of Example 1, mp >102 oC (decomp.); 'H NMR (DMSO-d) 8 3.02 3.11 (m, 2H), 3.19-3.26 (m, 2H), 3.29-3.36 (m, 2H), 3.37-3.49 (m, 3H), 3.54-3.64 10 (m, 2H), 3.72 (d, J = 11.0 Hz, 1H), 4.27 (d, J = 7.7 Hz, 1H), 4.39-4.65 (bs, 2H), 4.69 (ABq, J = 12.5 Hz, A6 = 0.20, 2H), 4.76-5.03 (bs, 1H), 5.01 (d, J = 3.7 Hz, 1H), 5.10 5.63 (bs, 4H), 7.37-7.43 (m, 4H); IR (KBr) 3340, 2920, 2890, 1625, 1600, 1490, 1450, 1400, 1365, 1150, 1075, 1030, and 820 cm-'; mass spectrum [(+) ESI], m/z 484.4/486.4 (M + NH4)*, Anal. Calcd. for C, 9

H

27 C10,, - 0.5 H 2 0: C, 47.96; H, 5.93; 15 N, 0.00, Found: C, 47.62; H, 5.82; N, 0.24. step 3 (4-Chloro)-benzyl-4',6'-O-benzylidene-p-D-maltoside The title compound was prepared as a white foam (1.20 g, 65%) from (4 20 chloro-benzyl)-p-D-maltoside using a procedure similar to Example 24, mp 187 188 0 C; 'H NMR (DMSO-d) 8 3.10 (t, J = 8.3 Hz, 1H), 3.27-3.41 (m, 4H), 3.46 (t, J = 8.8 Hz, 1H), 3.51-3.59 (m, 2H), 3.64-3.75 (m, 3H), 4.12 (dd, J = 3.1, 8.1 Hz, 1H), 4.29 (d, J = 7.7 Hz, 1H), 4.62-4.71 (bs, 1H), 4.70 (ABq, J = 12.5 Hz, A6 = 0.20, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.21-5.36 (bs, 2H), 5.47-5.55 (bs, 1H), 5.57 (s, 1H), 5.59 25 5.67 (bs, 1H), 7.34-7.39 (m, 3H), 7.39-7.46 (m, 6H); IR (KBr) 3570, 3430, 3080, 2870, 1615, 1495, 1450, 1435, 1375, 1360, 1340, 1255, 1160, 1120, 1070, 1030, 1000, and 755 cm'; mass spectrum [(+) ESI], m/z 555/557 (M + H)+, 572/574 (M +

NH

4 )*, 1126/1128 (2M + NH 4 ); Anal. Calcd. for C 26 H3 1 C10,: C, 56.27; H, 5.63; N, 0.00, Found: C, 56.09; H, 5.73; N, 0.23. 30 WO 00/31096 PCT/US99/27828 - 83 Example 69 Benzoic acid 1-O-(4-chloro)-benzyl-4',6'-O-benzylidene-6-deoxy-p-D-malto-6-yl ester The title compound was prepared as a white solid (0.800 g, 66%) from (4 5 chloro)-benzyl-4',6'-O-benzylidene-p-D-maltoside using a procedure similar to Example 2, mp >110 oC (decomp.); 'H NMR (DMSO-d) 6 3.16-3.23 (m, 1H), 3.27 3.43 (m, 2H), 3.49-3.64 (m, 4H), 3.68-3.78 (m, 2H), 4.02-4.08 (m, 1H), 4.35 (dd, J = 5.5, 12.5 Hz, 1H), 4.39 (d, J = 7.9 Hz, 1H), 4.57-4.62 (m, 1H), 4.67 (ABq, J = 12.5 Hz, A5 = 0.14, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.36 (dd, J = 5.1, 10.5 Hz, 2H), 5.52 (s, 10 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.80 (d, J = 6.2 Hz, 1H), 7.33-7.43 (m, 9H), 7.53 (t, J = 7.5 Hz, 2H), 7.66 (td, J = 1.1, 7.7 Hz, 1H), 7.99 (dd, J = 0.9, 8.1 Hz, 2H); IR (KBr) 3410, 2890, 1725, 1630, 1610, 1495, 1440, 1380, 1320, 1275, 1075, 1025, and 710 cm"; mass spectrum [(-) FAB], m/z 657/659 (M - H); Anal. Calcd. for C 33

H

35 C10, 2 . 1.0 H1 2 0: C, 58.54; H, 5.51; N, 0.00, Found: C, 58.75; H, 5.36; N, 0.14. 15 Example 70 4-Benzoyl-N- { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyll-2-chloro-phenvyI

I}

benzamide step 1 20 4-Benzoyl-N-{2-chloro-5-[(2,2',3,3',4',6,6'-hepta-O-acetyl-3-D-maltosyl)-oxy methyl]-phenyl}-benzamide The title compound was prepared as a white foam (0.240 g, 94%) from 2 chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenylamine using p-benzoyl benzoic acid and a procedure similar to step 1 of Example 65, mp >84 oC (decomp.); 25 'H NMR (DMSO-d) 5 1.93 (s, 3H), 1.94 (s, 6H), 1.97 (s, 6H), 2.01 (s, 3H), 2.08 (s, 3H), 3.93-4.03 (m, 4H), 4.15 (dd, J = 4.6, 12.3 Hz, 1H), 4.21 (dd, J = 4.6, 12.1 Hz, 1H), 4.39 (dd, J = 2.2, 11.9 Hz, 1H), 4.70 (ABq, J = 12.7 Hz, A8 = 0.14, 2H), 4.74 (dd, J = 8.1, 9.7 Hz, 1H), 4.86 (dd, J = 4.0, 10.5 Hz, 1H), 4.90 (d, J = 8.1 Hz, 1H), 4.98 (t, J = 9.7 Hz, 1H), 5.21 (dd, J = 9.7, 10.5 Hz, 1H), 5.28 (d, J = 4.0 Hz, 1H), 30 5.31 (dd, J = 8.6, 9.4 Hz, 1H), 7.22 (dd, J = 2.0, 8.3 Hz, 1H), 7.52 (d, J = 2.0 Hz, 1H), 7.55-7.62 (m, 3H), 7.69-7.74 (m, 1H), 7.76-7.80 (m, 2H), 7.85-7.88 (m, 2H), 8.11-8.14 (m, 2H), 10.30 (s, 1H); IR (KBr) 3400, 3010, 2950, 1755, 1675, 1650, WO 00/31096 PCT/US99/27828 - 84 1590, 1530, 1440, 1420, 1370, 1230, 1130, and 1040 cm'; mass spectrum [(+) FAB], m/z 984/986 (M + H)', 1006/1008 (M + Na)*, Anal. Calcd. for C 47

H

so C1NO 20 : C, 57.35; H, 5.12; N, 1.42, Found: C, 57.11; H, 5.03; N, 1.32. 5 step 2 4-Benzoyl-N-{2-chloro-5-[3,4-dihydroxy-6-hydroxymethyl-5-(3,4,5-trihydroxy-6 hydroxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxymethyl] phenyl}-benzamide The title compound was prepared as a off-white glassy solid (1.50 g, 95%) 10 from 4-benzoyl-N- { 2-chloro-5-[(2,2',3,3',4',6,6'-hepta-O-acetyl-p-D-maltosyl)-oxy methyl]-phenyl }-benzamide using a procedure similar to step 4 of Example 1, mp >131 oC (decomp.); 'H NMR (DMSO-d 6 ) 6 3.02-3.32 (m, 4H), 3.32-3.40 (m, 2H), 3.40-3.50 (m, 3H), 3.55-3.64 (m, 2H), 3.73 (d, J = 10.8 Hz, 1H), 4.31 (d, J = 7.9 Hz, 1H), 4.48-4.53 (bs, 1H), 4.53-4.59 (bs, 1H), 4.61 (d, J = 12.5 Hz, 1H), 4.83-4.92 (m, 15 3H), 5.02 (d, J = 4.0 Hz, 1H), 5.21-5.31 (bs, 1H), 5.36-5.48 (bs, 1H), 5.48-5.56 (bs, 1H), 7.32 (dd, J = 2.0, 8.3 Hz, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.56-7.62 (m, 3H), 7.69 7.74 (m, 1H), 7.78 (dd, J = 1.3, 8.3 Hz, 2H), 7.86 (d, J = 8.6 Hz, 2H), 8.14 (d, J = 8.6 Hz, 2H), 10.33 (s, 1H); IR (KBr) 3410, 2910, 1660, 1590, 1530, 1440, 1420, 1370, 1325, 1275, 1140, 1100, 1080, 1030, 910, and 710 cm'; mass spectrum [(+) FAB], 20 m/z 690/692 (M + H)', 712/714 (M + Na)*, Anal. Calcd. for C 33

H

3 6 CINO 3 * 1.0 -H 2 0: C, 55.97; H, 5.41; N, 1.98, Found: C, 55.98; H, 5.36; N, 1.97. step 3 4-Benzoyl-N-{5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro 25 phenyl}-benzamide The title compound was prepared as a white solid (1.07 g, 66%) from 4 benzoyl-N- { 2-chloro-5-[3,4-dihydroxy-6-hydroxymethyl-5-(3,4,5-trihydroxy-6 hydroxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yloxymethyl]-phenyl} benzamide using a procedure similar to Example 24, mp 208-211 oC; 'H NMR 30 (DMSO-d) 8 3.09-3.15 (m, 1H), 3.29-3.42 (m, 4H), 3.47 (td, J = 3.1, 8.8 Hz, 1H), 3.52-3.60 (m, 2H), 3.64-3.76 (m, 3H), 4.12 (dd, J = 3.1, 8.3 Hz, 1H), 4.34 (d, J = 7.7 Hz, 1H), 4.68 (t, J = 7.5 Hz, 1H), 4.75 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = WO 00/31096 PCTIUS99/27828 - 85 4.0 Hz, 1H), 5.30 (dd, J = 1.8, 5.3 Hz, 2H), 5.52 (d, J = 3.3 Hz, 1H), 5.57 (s, 1H), 5.63 (d, J = 6.6 Hz, 1H), 7.34-7.38 (m, 4H), 7.42-7.46 (m, 2H), 7.55 (d, J = 8.1 Hz, 1H), 7.56-7.62 (m, 3H), 7.69-7.74 (m, 1H), 7.76-7.80 (m, 2H), 7.87 (d, J = 8.3 Hz, 2H), 8.14 (d, J = 8.3 Hz, 2H), 10.33 (s, 1H); IR (KBr) 3410, 3070, 2920, 2860, 1655, 5 1590, 1530, 1445, 1425, 1380, 1330, 1275, 1145, 1070, 1030, 1000, 910, and 700 cm ; mass spectrum [(+) FAB], m/z 778/780 (M + H)', 800/802 (M + Na)*; Anal. Calcd. for C 4 0 ,H4C1NO, 3 - 0.5 H- 2 0: C, 61.03; H, 5.25; N, 1.78, Found: C, 61.11; H, 4.86; N, 1.74. 10 Example 71 4-Benzovl-N-{ 5- [(6-benzovl-oxy-4',6'-O-benzylidene--D-maltosvyl)-oxv-methyll-2 chloro-phenyl } -benzoic acid amide The title compound was prepared as a white solid (0.352 g, 63%) from 4 benzoyl-N- { 5-[(4',6'-O-benzylidene-3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl } 15 benzamide using a procedure similar to Example 2, mp >135 oC (decomp.); 1H NMR (DMSO-d) 8 3.18-3.24 (m, 1H), 3.32-3.43 (m, 2H), 3.50-3.65 (m, 4H), 3.72 (td, J = 5.3, 10.1 Hz, 1H), 3.77-3.82 (m, 1H), 4.05 (dd, J = 4.8, 10.1 Hz, 1H), 4.36 (dd, J = 4.8, 12.1 Hz, 1H), 4.43 (d, J = 7.9 Hz, 1H), 4.62 (d, J = 10.3 Hz, 1H), 4.72 (ABq, J = 12.7 Hz, A6 = 0.14, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.32-5.37 (m, 1H), 5.40 (d, J = 4.4 20 Hz, 1H), 5.52 (s, 1H), 5.59 (s, 1H), 5.80 (d, J = 5.5 Hz, 1H), 7.31-7.37 (m, 4H), 7.39 7.43 (m, 2H), 7.48-7.53 (m, 3H), 7.56-7.66 (m, 4H), 7.71 (tt, J = 1.1, 6.8 Hz, 1H), 7.77 (dd, J = 1.1, 7.9 Hz, 2H), 7.85 (d, J = 8.6 Hz, 2H), 7.99 (dd, J = 0.9, 8.1 Hz, 2H), 8.12 (d, J = 8.6 Hz, 2H), 10.33 (s, 1H); IR (KBr) 3420, 3080, 2850, 1720, 1660, 1600, 1530, 1440, 1420, 1370, 1320, 1275, 1140, 1070, 1030, and 715 cm'; mass 25 spectrum [(+) FAB], m/z 882 (M + H)+, 904/906 (M + Na)*; Anal. Calcd. for

C

4 7

H

4 C1NO, 4 . - 1.0 H20: C, 62.70; H, 5.15; N, 1.56, Found: C, 62.83; H, 5.02; N, 1.70.

WO 00/31096 PCT/US99/27828 - 86 Example 72 4-Benzovl-N- { 5-[(4'.6'-O-benzylidene-6-O-(2-iodo)-benzoyl-B-D-maltosyl)-oxy methyll-2-chloro-phenvyl } -benzamide The title compound was prepared as a white solid (0.145 g, 32%) from 4 5 benzoyl-N- { 5-[(4' .6' -O-benzylidene-o-D-maltosyl)-oxy-methyl]-2-chloro-phenyl

}

benzamide using o-I-BzC1 and a procedure similar to Example 2, mp >122 oC (decomp.); 'H NMR (DMSO-d) 8 3.16-3.23 (m, 1H), 3.28-3.45 (m, 2H), 3.49-3.67 (m, 4H), 3.75 (dd, J = 4.8, 7.5 Hz, 1H), 3.78-3.84 (m, 1H), 4.14 (dd, J = 4.6, 9.7 Hz, 1H), 4.36 (dd, J = 5.5, 12.1 Hz, 1H), 4.44 (d, J = 7.7 Hz, 1H), 4.61-4.67 (m, 1H), 10 4.73 (ABq, J = 12.7 Hz, A8 = 0.15, 2H), 5.16 (d, J = 4.0 Hz, 1H), 5.38 (dd, J = 5.3, 10.5 Hz, 2H), 5.55 (s, 1H), 5.60 (d, J = 2.6 Hz, 1H), 5.88 (d, J = 6.2 Hz, 1H), 7.26 (td, J = 1.8, 7.9 Hz, 1H), 7.31-7.38 (m, 4H), 7.40-7.45 (m, 2H), 7.48-7.53 (m, 2H), 7.56-7.62 (m, 3H), 7.71 (tt, J = 1.3, 6.8 Hz, 1H), 7.75-7.79 (m, 3H), 7.85 (dd, J = 1.8, 6.6 Hz, 2H), 8.00 (dd, J = 1.1, 8.1 Hz, 1H), 8.12 (dd, J = 1.8, 6.6 Hz, 2H), 10.30 (s, 15 1H); IR (KBr) 3410, 3070, 2850, 1730, 1655, 1590, 1525, 1440, 1420, 1375, 1280, 1250, 1140, 1070, 1025, and 705 cm'; mass spectrum [(+) FAB], m/z 1008 (M + H)', 1030 (M + Na):; Anal. Calcd. for C 47 H1 4 3 CINO 4 * 0.5 H 2 0: C, 55.50; H, 4.36; N, 1.38, Found: C, 55.14; H, 4.22; N, 1.36. 20 Example 73 4-Benzovl-N-{ 5-[(4'.6'-O-benzvlidene-6-O-(3-iodo-benzovl)-p-D-maltosvl)-oxy methyl]l-2-chloro-phenvl } -benzamide The title compound was prepared as a white solid (0.244 g, 54%) from 4 benzoyl-N-{5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl} 25 benzamide using m-I-BzCl (prepared from m-I-benzoic acid and oxalyl chloride) and a procedure similar to Example 2, mp 185-188.5 oC; 'H NMR (DMSO-d) 8 3.18 3.24 (m, 1H), 3.27-3.43 (m, 2H), 3.50-3.63 (m, 4H), 3.71 (td, J = 4.6, 9.9 Hz, 1H), 3.77-3.82 (m, 1H), 4.06 (dd, J = 4.8, 9.9 Hz, 1H), 4.35 (dd, J = 5.5, 12.1 Hz, 1H), 4.44 (d, J = 7.7 Hz, 1H), 4.61-4.67 (m, 1H), 4.73 (ABq, J = 12.5 Hz, A8 = 0.13, 2H), 30 5.14 (d, J = 4.0 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.39 (d, J = 5.1 Hz, 1H), 5.53 (s, 1H), 5.58 (d, J = 2.9 Hz, 1H), 5.79 (d, J = 6.2 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.33-7.37 (m, 4H), 7.38-7.43 (m, 2H), 7.51 (d, J = 8.1 Hz, 1H), 7.56-7.62 (m, 3H), WO 00/31096 PCT/US99/27828 - 87 7.71 (tt, J = 1.3, 6.8 Hz, 1H), 7.76-7.80 (m, 2H), 7.85 (dd, J = 1.8, 6.6 Hz, 2H), 7.99 (dt, J = 1.5, 7.7 Hz, 2H), 8.11 (dd, J = 1.8, 6.8 Hz, 2H), 8.25 (t, J = 1.8 Hz, 1H), 10.29 (s, 1H); IR (KBr) 3410, 3080, 2910, 2850, 1725, 1650, 1590, 1570, 1530, 1440, 1420, 1375, 1280, 1255, 1140, 1070, 1030, 750, and 700 cm ; mass spectrum 5 [(+) FAB], m/z 1030 (M + Na) ; Anal. Calcd. for C 4 7

H

43

CINO

1 4 - 0.5 H 2 0: C, 55.50; H, 4.36; N, 1.38, Found: C, 55.13; H, 4.15; N, 1.38. Example 74 4-Benzovl-N- {5-[(4'.6'-O-benzvlidene-6-(4-iodo-benzo1)-oxy- B-D-maltosvl)-oxy 10 methyll-2-chloro-phenyll}-benzoic acid amide The title compound was prepared as a white solid (0.378 g, 59%) from 4 benzoyl-N- { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl } benzamide using p-iodobenzoyl chloride and a procedure similar to Example 2, mp >151 oC (decomp.); IH NMR (DMSO-d) 8 3.18-3.24 (m, 1H), 3.32-3.42 (m, 2H), 15 3.49-3.63 (m, 4H), 3.71 (td, J = 4.8, 9.9 Hz, 1H), 3.78 (ddd, J = 1.1, 4.6, 9.2 Hz, 1H), 4.04 (dd, J = 4.8, 9.9 Hz, 1H), 4.35 (dd, J = 4.8, 12.1 Hz, 1H), 4.42 (d, J = 7.7 Hz, 1H), 4.59 (d, J = 10.8 Hz, 1H), 4.72 (ABq, J = 12.7 Hz, A8 = 0.13, 2H), 5.13 (d, J = 4.0 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.39 (d, J = 5.1 Hz, 1H), 5.52 (s, 1H), 5.59 (d, J = 2.4 Hz, 1H), 5.82 (d, J = 5.9 Hz, 1H), 7.31-7.37 (m, 4H), 7.38-7.42 (m, 2H), 7.51 20 (d, J = 8.3 Hz, 1H), 7.56-7.61 (m, 3H), 7.69-7.75 (m, 3H), 7.76-7.79 (m, 2H), 7.85 (d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 8.6 Hz, 2H), 10.30 (s, 1H); IR (KBr) 3420, 3080, 2890, 2840, 1725, 1655, 1590, 1530, 1440, 1420, 1380, 1365, 1325, 1280, 1160, 1120, 1070, 1030, 1005, 750, and 700 cm'; mass spectrum [(+) FAB], m/z 1030/1032 (M + Na)+; Anal. Calcd. for C 4 7

H

43 C1INO 4 : C, 55.01; H, 4.42; 25 N, 1.36, Found: C, 54.99; H, 4.38; N, 1.40.

WO 00/31096 PCT/US99/27828 - 88 Example 75 (1-f 5- [(4' .6'- O-Benzvlidene- p -D-maltosyl)-oxv-methvyll-2-chloro-phenyl carbamovyl }I ethyl)-carbamic acid 9H-fluoren-9ylmethyl ester step 1 5 N-{ 2 -Chloro-5-[(2,2',3,3',4',6,6')-hepta-O-acetyl-qp-D-maltosyl-oxymethyl] phenyl}-(9H-fluoren-9-ylmethoxycarbonyl)-L-alaninamide The title compound was prepared as a white foam (2.50 g, 36%) from 2 chloro-5-(hepta-O-acetyl--D-maltosyl-oxymethyl)-phenylamine using N-(9H fluoren-9-ylmethyoxycarbonylamino)-L-alanine and a procedure similar to step 1 of 10 Example 65, mp >96 oC (decomp.); 'H NMR (DMSO-d) a 1.33 (dd, J= 7.2 Hz, 3H), 1.918 (s, 3H), 1.919 (s, 3H), 1.94 (s, 3H), 1.966 (s, 3H), 1.97 (s, 3H), 2.01 (s, 3H), 2.07 (s, 3H), 3.91-4.02 (m, 4H), 4.12-4.24 (m, 3H), 4.24-4.34 (m, 3H), 4.34-4.40 (m, 1H), 4.53 (d, J = 12.7 Hz, 1H), 4.68-4.75 (m, 2H), 4.84 (d, J = 4.0 Hz, 1H), 4.86 (d, J = 2.6 Hz, 1H), 4.97 (t, J = 9.7 Hz, 1H), 5.21 (t, J = 9.7 Hz, 1H), 5.27 (d, J = 3.7 Hz, 15 1H), 5.27-5.32 (m, 1H), 7.08 (dd, J = 1.8, 8.1 Hz, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.47 (d, J = 8.1 Hz, 1H), 7.69-7.78 (m, 4H), 7.88 (d, J = 7.5 Hz, 2H), 9.42 (s, 1H); IR (KBr) 3360, 3010, 2950, 1755, 1590, 1535, 1440, 1420, 1370, 1230, 1050, and 755 cm'; mass spectrum [(+) ESI], m/z 1069.2 (M + H)', 1086.2/1088.2 (M + NH 4 )', Anal. Calcd. for C, 51

H

5 7 C1N 2 0 2 1 3.5 HO: C, 54.09; H, 20 5.70; N, 2.47, Found: C, 53.67; H, 5.11; N, 2.34. step 2 N-[2-Chloro-5-(P3-D-maltosyl-oxymethyl)-phenyl]-(9H-fluoren-9 ylmethoxycarbonyl)-L-alaninamide 25 To a stirred solution of KCN (0.032 g, 0.491 mmol) in MeOH (10 mL) at 0oC was added (1- { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl carbamoyl}ethyl)-carbamic acid 9H-fluoren-9ylmethyl ester (1.05 g, 0.982 mmol). The reaction mixture was stirred at this temperature for 24 h and then concentrated. The resulting residue was diluted with THF:sat. aq. NaHCO 3 (1:1, 20 mL) followed 30 by addition of Fmoc-CI (0.170 g, 0.658 mmol). This solution was stirred at rt for 0.5 h, and the resulting mixture filtered to remove the solid that formed. The filtrate was concentrated, and the residue was purified by flash chromatgraphy (80:2:1 to 4:2:1 WO 00/31096 PCT/US99/27828 - 89 EtOAc:EtOH: H 2 0) to afford the product (0.600 g, 79%) which was used in the next step without further purification. step 3 5 (1-{5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl carbamoyl}ethyl)-carbamic acid 9H-fluoren-9ylmethyl ester The title compound was prepared as a off-white solid (0.295 g, 41%) from N [2-chloro-5-(p-D-maltosyl-oxymethyl)-phenyl] -(9H-fluoren-9-ylmethoxycarbonyl)-L alaninamide using a procedure similar to Example 24, mp >190 oC (decomp.); 'H 10 NMR (DMSO-d) 8 1.34 (d, J = 7.0 Hz, 3H), 3.06-3.14 (m, 1H), 3.28-3.42 (m, 3H), 3.41 (td, J = 2.2, 9.2 Hz, 1H), 3.51-3.60 (m, 2H), 3.64-3.76 (m, 4H), 4.11 (dd, J = 2.4, 7.7 Hz, 1H), 4.22 (t, J = 6.6 Hz, 1H), 4.26-4.35 (m, 4H), 4.67 (t, J = 5.7 Hz, 1H), 4.69 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.26 (d, J = 4.8 Hz, 1H), 5.31 (d, J = 5.1 Hz, 1H), 5.52 (d, J = 2.6 Hz, 1H), 5.57 (s, 1H), 5.64 (d, J = 6.2 15 Hz, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.28-7.48 (m, 10H), 7.69-7.79 (m, 4H), 7.88 (d, J = 7.5 Hz, 2H), 9.46 (s, 1H); IR (KBr) 3390, 3080, 2920, 2870, 2350, 1705, 1590, 1525, 1445, 1420, 1375, 1340, 1310, 1255, 1140, 1070, 1030, and 740 cm-'; mass spectrum [(+) ESI], m/z 880 (M + NH); Anal. Calcd. for C 44

H

47 C1N 2 04 1.0 H20: C, 59.96; H, 5.60; N, 3.18, Found: C, 60.23; H, 5.53; N, 3.45. 20 Example 76 N-(9H-Fluoren-9ylmethoxvcarbonvyl)-N'- { 5-[(6- O-benzoyl-4',6'-O-benz1idene-p-D maltosyl)-oxy-methyll-2-chloro-phenyl }-L-alaninamide The title compound was prepared as a white solid (0.083 g, 62%) from (1-{5 25 [(4',6'-O-benzylidene-p3-D-maltosyl)-oxy-methyl]-2-chloro-phenylcarbamoyl } ethyl) carbamic acid 9H-fluoren-9ylmethyl ester using a procedure similar to Example 2, mp 224-226 oC; 'H NMR (DMSO-d) 8 1.32 (d, J = 7.2 Hz, 3H), 3.19 (t, J = 8.3 Hz, 1H), 3.26-3.37 (m, 4H), 3.48-3.63 (m, 3H), 3.70 (dd, J = 5.1, 9.9 Hz, 1H), 3.73-3.78 (m, 1H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H), 4.21 (t, J = 6.8 Hz, 1H), 4.24-4.38 (m, 3H), 30 4.40 (d, J = 7.7 Hz, 1H), 4.56-4.63 (m, 1H), 4.65 (ABq, J = 12.5 Hz, A = 0.15, 2H), 5.13 (d, J = 3.7 Hz, 1H), 5.27-5.41 (bs, 2H), 5.52 (s, 1H), 5.54-5.61 (bs, 1H), 5.75 5.84 (bs, 1H), 7.21 (d, J = 8.6 Hz, 1H), 7.28-7.37 (m, 5H), 7.37-7.45 (m, 5H), 7.51 (t, WO 00/31096 PCT/US99/27828 - 90 J = 7.9 Hz, 2H), 7.63 (t, J = 7.5 Hz, 1H), 7.68-7.77 (m, 4H), 7.88 (d, J = 7.7 Hz, 2H), 7.98 (d, J = 7.2 Hz, 2H), 9.43 (s, 1H); IR (KBr) 3400, 3080, 2920, 2850, 1725, 1590, 1530, 1440, 1420, 1375, 1320, 1275, 1070, 1025, 745, and 715 cm'; mass spectrum [(+) FAB], m/z 989/991 (M + Na)+; Anal. Calcd. for C 5 1 H 5 C1N 2 015 1.0 H 2 0: C, 5 62.16; H, 5.42; N, 2.84, Found: C, 61.99; H, 5.23; N, 3.06. Example 77 N'- { 5-[(6-O-benzoyl-4'.6'-O-benzylidene- 3-D-maltosyl)-oxy-methyl]-2-chloro phenvyl I -L-alaninamide 10 To a stirred solution of 20% piperidine (2.00 mL, 20.2 mmol) in DMF (10 mL) at rt was added N-(9H-fluoren-9ylmethoxycarbonyl)-N'-{5-[(6-O-benzoyl-4',6' O-benzylidene-p3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl}-L-alaninamide (0.300 g, 0.256 mmol). After 2 h at this temperature, the solution was concentrated on the high vacuum. The residue was purified by preparatory plate chromatography (10:2:1 15 EtOAc:EtOH:H,O) to afford the product (0.018 g, 78%) as an off-white solid, mp 131-133 oC; 'H NMR (DMSO-d) 8 1.26 (d, J = 7.0 Hz, 3H), 3.15-3.22 (m, 1H), 3.26-3.42 (m, 5H), 3.47-3.64 (m, 4H), 3.70 (dd, J = 4.6, 9.7 Hz, 1H), 3.73-3.79 (m, 1H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H), 4.35 (dd, J = 5.1, 12.1 Hz, 1H), 4.40 (d, J = 7.7 Hz, 1H), 4.60 (d, J = 12.7 Hz, 1H), 4.66 (ABq, J = 12.3 Hz, A6 = 0.14, 2H), 5.13 (d, J 20 = 3.7 Hz, 1H), 5.34 (dd, J = 0.9, 5.3 Hz, 2H), 5.52 (s, 1H), 5.57 (d, J = 2.9 Hz, 1H), 5.80 (d, J = 6.2 Hz, 1H), 7.15 (dd, J = 2.0, 8.1 Hz, 1H), 7.33-7.38 (m, 3H), 7.38-7.45 (m, 3H), 7.53 (t, J = 7.7 Hz, 2H), 7.63-7.68 (m, 2H), 7.98 (d, J = 1.3 Hz, 1H), 8.00 (s, 1H), 8.20 (s, 1H); IR (KBr) 3410, 2920, 2850, 1720, 1625, 1590, 1525, 1445, 1420, 1375, 1275, 1070, 1025, and 715 cm'; mass spectrum [(+) FAB], m/z 745 (M + H)+, 25 767 (M + Na)'; Anal. Calcd. for C 36 H4 1 C1N 2 0,1 3 . 2.0 H 2 0: C, 55.35; H, 5.81; N, 3.59, Found: C, 55.63; H, 5.77; N, 3.23.

WO 00/31096 PCT/US99/27828 -91 Example 78 N- { 5- [(4' ,6'- O-Benzvlidene- 3-D-maltosyl)-oxvmethyll-2-chloro-phenvl } -N-methyl acetamide step 1 5 N-[ 5

-(

2

,

2

',

3 ,3', 4 ',6,6'-Hepta-O-acetyl-p-D-maltosyl)-oxy.methyl-2-chloro phenyl]-N-methyl-acetamide To a stirred solution of N-[2-chloro-5-(hepta-O-acetyl-p3-D-maltosyl oxymethyl)-phenyl]-acetamide (0.100 g, 0.122 mmol) in THF (2.0 mL) at -78 oC was added NaHMSA (0.183 mL, 1.0 M in THF). After 0.5 h at this temperature, methyl 10 iodide (0.0152 mL, 0.244 mmol) was added, and the reaction was warmed to rt for 2 h. At this point, the reaction was diluted with EtOAc (100 mL), washed with 1 N HCI (10 mL), sat. aq. NaHCO 3 (10 mL), and brine (10 mL), and then dried (MgSO 4 ). After concentration, the resulting oilly residue was purified by preparatory plate chromatography using 50:50 EtOAc:petroleum ether as the eluant to afford the 15 product (0.0408 g, 40%) as a white foam, mp >252 oC (decomp.); 'H NMR (CDCl 3 ) 8 1.81 (s, 3H), 2.00 (s, 3H), 2.01 (s, 6H), 2.02 (s, 3H), 2.04 (s, 3H), 2.10 (s, 3H), 2.15 (s, 3H), 3.19 (d, J = 2.9 Hz, 3H), 3.67-3.72 (min, 1H), 3.94-3.99 (m, 1H), 4.03 (t, J = 9.4 Hz, 1H), 4.07 (d, J = 2.2 Hz, 1H), 4.21-4.28 (min, 2H), 4.54 (dd, J = 2.9, 12.3 Hz, 1H), 4.59 (d, J = 11.6 Hz, 1H), 4.64 (d, J = 7.5 Hz, 1H), 4.83-4.93 (min, 3H), 5.06 (t, J 20 = 10.1 Hz, 1H), 5.26 (td, J = 3.3, 9.0 Hz, 1H), 5.36 (t, J = 9.7 Hz, 1H), 5.42 (d, J = 4.0 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.24 (dt, J = 2.0, 8.1 Hz, 1H), 7.47 (dd, J = 1.1, 8.1 Hz, 1H); IR (KBr) 3470, 2950, 1755, 1620, 1480, 1420, 1380, 1230, 1140, and 1045 cm-'; mass spectrum [(+) ESI], m/z 832 (M + H)', Anal. Calcd. for C 36

H

46 C1NO, 9 . 1.5 IH O: C, 50.32; H, 5.75; N, 1.63, Found: C, 50.17; H, 5.38; N, 1.67. 25 step 2 N-{2-Chloro-5-[(p-D-maltosyl)-oxymethyl]-phenyl}-N-methyl-acetamide The title compound was prepared as a white solid (0.475 g, 99%) from N-[5 (2,2',3,3',4' ,6,6'-hepta-O-acetyl-p3-D-maltosyl)-oxy-methy1-2-chloro-phenyl]-N 30 methyl-acetamide using a procedure similar to step 4 of Example 1, mp >96 oC (decomp.); 'H NMR (DMSO-d 6 ) 6 1.67 (s, 3H), 3.05 (d, J = 1.1 Hz, 3H), 3.06-3.14 (min, 1H), 3.18-3.28 (m, 2H), 3.30-3.38 (min, 2H), 3.38-3.49 (min, 4H), 3.53-3.63 (inm, WO 00/31096 PCT/US99/27828 - 92 2H), 3.68-3.75 (m, 1H), 4.28 (dd, J = 7.9, 9.7 Hz, 1H), 4.48-4.53 (m, 2H), 4.62 (dd, J = 3.3, 13.2 Hz, 1H), 4.84 (d, J = 13.0 Hz, 1H), 4.89 (dd, J = 5.5, 7.7 Hz, 2H), 5.01 (d, J = 3.7 Hz, 1H), 5.30 (dd, J = 4.8, 7.7 Hz, 1H), 5.42 (dd, J = 2.4, 6.2 Hz, 1H), 5.52 (d, J = 3.1 Hz, 1H), 7.43 (dt, J = 1.8, 8.1 Hz, 1H), 7.57 (s, 1H), 7.60 (d, J = 8.3 Hz, 5 1H); IR (KBr) 3400, 3000, 2910, 1645, 1580, 1480, 1420, 1385, 1320, 1255, 1195, 1145, 1120, 1075, 1035, and 755 cm'; mass spectrum [(+) FAB], m/z 538 (M + H)+, 560 (M + Na)', Anal. Calcd. for C 2 2

H

3 2 C1NO12, 1.0 HO: C, 47.53; H, 6.16; N, 2.52, Found: C, 47.18; H, 6.01; N, 2.38. 10 step 3 N-{5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxymethyl]-2-chloro-phenyl}-N methyl-acetamide The title compound was prepared as a white foam (0.315 g, 63%) from N-{2 chloro-5-[(P-D-maltosyl)-oxymethyl]-phenyl}-N-methyl-acetamide using a procedure 15 similar to Example 24, mp >125 oC (decomp.); 'H NMR (DMSO-d) 6 1.68 (d, J = 1.3 Hz, 3H), 3.06 (d, J = 1.3 Hz, 3H), 3.09-3.16 (m, 1H), 3.28-3.42 (m, 4H), 3.42 3.50 (m, 1H), 3.50-3.60 (m, 2H), 3.64-3.75 (m, 3H), 4.09-4.14 (m, 1H), 4.30 (dd, J = 7.7, 10.3 Hz, 1H), 4.60-4.69 (m, 2H), 4.85 (d, J = 13.2 Hz, 1H), 5.14 (d, J = 4.0 Hz, 1H), 5.30 (d, J = 5.1 Hz, 1H), 5.33 (dd, J = 5.1, 7.9 Hz, 1H), 5.53 (d, J = 3.3 Hz, 1H), 20 5.57 (s, 1H), 5.63 (dd, J = 2.9, 6.8 Hz, 1H), 7.34-7.38 (m, 3H), 7.41-7.46 (m, 3H), 7.58 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H); IR (KBr) 3410, 2920, 2860, 1640, 1610, 1580, 1480, 1440, 1410, 1380, 1320, 1185, 1150, 1070, 1030, 955, and 755 cm'; mass spectrum [(-) FAB], m/z 624 (M - H); Anal. Calcd. for C 29

H

3 6

CINO

1 2 2.5 H 2 0: C, 51.90; H, 6.16; N, 2.09, Found: C, 51.92; H, 5.48; N, 2.09. 25 Example 79 N- { 5-[(6-O-Benzovl-4', 6'-O-benzvlidene- p-D-maltosyl)-oxvmethyll-2-chloro phenv1 I -N-methyl-acetamide The title compound was prepared as a white solid (0.087 g, 37%) from N-{5 30 [(4',6'-O-benzylidene-p3-D-maltosyl)-oxymethyl]-2-chloro-phenyl}-N-methyl acetamide using a procedure similar to Example 2, mp 180-183 oC; 'H NMR (DMSO-d) 6 1.64 (d, J = 4.0 Hz, 3H), 3.02 (s, 3H), 3.17-3.25 (m, 1H), 3.35 (d, J = WO 00/31096 PCT/US99/27828 - 93 9.4 Hz, 1H), 3.37-3.43 (m, 1H), 3.49-3.65 (m, 4H), 3.70 (dd, J = 4.6, 9.9 Hz, 1H), 3.73-3.79 (m, 1H), 4.04 (d, J = 5.1, 9.9 Hz, 1H), 4.34 (ddd, J = 2.4, 4.8, 12.1 Hz, 1H), 4.41 (dd, J = 7.9, 10.1 Hz, 1H), 4.58 (d, J = 11.4 Hz, 1H), 4.72 (ABq, J = 12.5 Hz, A6 = 0.12, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.34 (d, J = 4.8 Hz, 1H), 5.43 (dd, J = 5 5.3, 7.2 Hz, 1H), 5.52 (s, 1H), 5.59 (d, J = 2.6 Hz, 1H), 5.79 (dd, J = 2.0, 5.7 Hz, 1H), 7.33-7.37 (m, 3H), 7.38-7.43 (m, 3H), 7.50-7.55 (m, 3H), 7.56 (d, J = 8.3 Hz, 1H), 7.63-7.68 (m, 1H), 7.96-8.00 (m, 2H); IR (KBr) 3495, 3400, 3090, 2930, 2890, 1730, 1645, 1600, 1575, 1480, 1445, 1420, 1385, 1360, 1320, 1270, 1200, 1160, 1110, 1070, 1050, 1020, 985, and 715 cm 1 ; mass spectrum [(+) FAB], m/z 730 (M + 10 H)', 752 (M + Na)'; Anal. Calcd. for C 36

H

40 CINO,3. H-O: C, 59.22; H, 5.52; N, 1.92, Found: C, 59.02; H, 5.50; N, 1.79. Example 80 N- {5-[(4'.6'-O-Benzylidene- -D-maltosvyl)-oxy-methyl]l-2-chloro-phenvlI -carbamic 15 acid methyl ester step 1

N-{

5

-[(

2

,

2 ',3,3',4',6,6'-Hepta-O-acetyl-p-D-maltosyl)-oxymethyl]-2.-chloro phenyl}-carbamic acid methyl ester To a stirred solution of 2-chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl) 20 phenylamine (1.40 g, 1.80 mmol) in THF (18 mL) at 0 oC was added NaH (0.108 g, 2.70 mmol). After 10 min. at this temperature, methyl chloroformate (0.167 mL, 2.16 mmol) was added, and then the reaction was warmed to rt for 3 h. At this point, the reaction was concentrated, and the residue was diluted with EtOAc (300 mL). This solution was washed with IN HC1 (30 mL), sat. aq. NaHCO 3 (30mL), and brine (30 25 mL) and then dried (MgSO 4 ). After concentration, the resulting oilly residue was purified by flash chromatography (2:98 to 10:90 acetone:CHC13 gradient) to afford the product (1.33 g, 88%) as a white foam, mp >79 oC (decomp.); 'H NMR (DMSO d 6 ) 8 1.93 (s, 3H), 1.94 (s, 6H), 1.970 (s, 3H), 1.973 (s, 3H), 2.01 (s, 3H), 2.08 (s, 3H), 3.64 (s, 3H), 3.91-4.03 (m, 4H), 4.12-4.23 (m, 2H), 4.38 (dd, J = 1.8, 11.9 Hz, 30 1H), 4.54 (d, J = 12.7 Hz, 1H), 4.69-4.75 (m, 2H), 4.83-4.88 (m, 2H), 4.97 (t, J = 9.7 Hz, 1H), 5.21 (dd, J = 9.7, 10.3 Hz, 1H), 5.27 (d, J = 3.7 Hz, 1H), 5.30 (dd, J = 8.6, 9.2 Hz, 1H), 7.07 (dd, J = 2.0, 8.3 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.48 (d, J = 1.8 WO 00/31096 PCT/US99/27828 - 94 Hz, 1H), 9.08 (s, 1H); IR (KBr) 3420, 2950, 1755, 1590, 1530, 1450, 1420, 1375, 1230, 1130, and 1040 cm'; mass spectrum [(+) FAB], m/z 834 (M + H)', 856 (M + Na)*, Anal. Calcd. for C 35

H

4 4 C1NO 2 0 . 0.5 HO: C, 49.86; H, 5.38; N, 1.66, Found: C, 49.68; H, 5.14; N, 1.58. 5 step 2 {2-Chloro-5-[(p-D-maltosyl)-oxy-methyl]-phenyl}-carbamic acid methyl ester The title compound was prepared as a white foam (0.753 g, 99%) from N-{5 [(2,2',3,3',4',6,6'-hepta-O-acetyl-p-D-maltosyl)-oxymethyl]-2-chloro-phenyl

}

10 carbamic acid methyl ester using a procedure similar to step 2 of Example 63, mp >109 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 3.01-3.11 (m, 2H), 3.19-3.27 (m, 2H), 3.28-3.38 (m, 2H), 3.38-3.50 (m, 3H), 3.52-3.64 (m, 2H), 3.64 (s, 3H), 3.72 (d, J = 11.2 Hz, 1H), 4.28 (d, J = 7.9 Hz, 1H), 4.44-4.57 (m, 2H), 4.67 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 4.83-4.96 (bs, 2H), 5.01 (d, J = 4.0 Hz, 1H), 5.16-5.32 (bs, 1H), 5.34 15 5.58 (bs, 2H), 7.21 (dd, J = 2.0, 8.1 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 9.07 (s, 1H); IR (KBr) 3420, 2920, 1725, 1590, 1530, 1450, 1425, 1370, 1310, 1255, 1230, 1140, 1070, and 1030 cm-'; mass spectrum [(+) FAB], m/z 562/564 (M + Na)*, Anal. Calcd. for C 21

H

30 C1N0,3 * 0.5 H20: C, 45.95; H, 5.69; N, 2.55, Found: C, 45.81; H, 5.82; N, 2.39. 20 step 3 N-{5-[(4',6'-O-Benzylidene-3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl} carbamic acid methyl ester The title compound was prepared as a white solid (0.552 g, 71%) from {2 25 chloro-5-[(p-D-maltosyl)-oxy-methyl]-phenyl}-carbamic acid methyl ester using a procedure similar to Example 24, mp 142-145 oC; 'H NMR (DMSO-d

,

) 6 3.06-3.13 (m, 1H), 3.28-3.41 (m, 4H), 3.46 (td, J = 2.4, 8.8 Hz, 1H), 3.50-3.61 (in, 2H), 3.65 (s, 3H), 3.65-3.75 (m, 3H), 4.11 (dd, J = 3.1, 8.1 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.64 4.69 (m, 1H), 4.68 (ABq, J = 12.5 Hz, A6 = 0.22, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.26 30 (d, J = 5.1 Hz, 1H), 5.30 (d, J = 4.8 Hz, 1H), 5.51 (d, J = 2.9 Hz, 1H), 5.57 (s, 1H), 5.63 (d, J = 6.4 Hz, 1H), 7.22 (dd, J = 2.0, 8.1 Hz, 1H), 7.34-7.38 (m, 3H), 7.41-7.46 (m, 3H), 7.54 (d, J = 1.8 Hz, 1H), 9.07 (s, 1H); IR (KBr) 3530, 3410, 2920, 2850, WO 00/31096 PCT/US99/27828 - 95 1730, 1590, 1535, 1450, 1420, 1375, 1310, 1250, 1230, 1145, 1075, 1030, and 1000 cm ; mass spectrum [(+) FAB], m/z 650/652 (M + Na)+; Anal. Calcd. for

C,

8

H

3 4 C1NO13 * 0.5 H20: C, 52.79; H, 5.54; N, 2.20, Found: C, 52.85; H, 5.77; N, 2.11. 5 Example 81 N- { 5- [(6- O-Benzoyl-4',6'-O-benzylidene- B-D-maltosyl)-oxy-methyl] -2-chloro phenvl }-carbamic acid methyl ester The title compound was prepared as a white solid (0.407 g, 71%) from N-{5 10 [(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl } -carbamic acid methyl ester using a procedure similar to Example 2, mp >103 oC (decomp.); 'H NMR (DMSO-d) 6 3.16-3.22 (m, 1H), 3.27-3.42 (m, 2H), 3.48-3.63 (m, 4H), 3.63 (s, 3H), 3.70 (dd, J = 5.1, 10.1 Hz, 1H), 3.73-3.79 (m, 1H), 4.05 (dd, J = 4.8, 9.9 Hz, 1H), 4.35 (dd, J = 5.1, 12.1 Hz, 1H), 4.40 (d, J = 7.7 Hz, 1H), 4.58-4.63 (m, 1H), 15 4.66 (ABq, J = 12.5 Hz, AS = 0.14, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.35 (dd, J = 5.3, 8.3 Hz, 2H), 5.52 (s, 1H), 5.57 (d, J = 3.1 Hz, 1H), 5.80 (d, J = 6.2 Hz, 1H), 7.19 (dd, J = 2.0, 8.1 Hz, 1H), 7.33-7.43 (m, 6H), 7.50-7.55 (m, 3H), 7.63-7.68 (m, 1H), 8.00 (dd, J = 1.1, 8.1 Hz, 2H), 9.05 (s, 1H); IR (KBr) 3420, 3080, 2920, 2860, 1725, 1640, 1590, 1530, 1445, 1425, 1370, 1320, 1275, 1220, 1140, 1070, 1025, and 720 cm'; 20 mass spectrum [(+) ESI], m/z 732/734 (M + H)', 754/756 (M + Na)*; Anal. Calcd. for

C

3 5 HC1NO, 4 : C, 57.42; H, 5.23; N, 1.91, Found: C, 57.17; H, 5.26; N, 1.81. Example 82 N-f 5-[(6-O-(3-Benzvyl-l-oxo-propyl)-4'.6'-O-benzvlidene--D-maltosvl)-oxy 25 methyll-2-chloro-phenvl }-carbamic acid methyl ester The title compound was prepared as a white solid (0.152 g, 42%) from N-{5 [(4',6'-O-benzylidene-3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl }-carbamic acid methyl ester using hydrocinnamoyl chloride and a procedure similar to Example 2, mp >93 'C (decomp.); 'H NMR (DMSO-d 6 ) 8 2.66 (t, J = 7.7 Hz, 2H), 2.84 (t, J = 7.7 30 Hz, 2H), 3.08-3.16 (m, 1H), 3.27-3.49 (m, 4H), 3.53-3.60 (m, 2H), 3.62-3.72 (m, 2H), 3.63 (s, 3H), 4.05-4.13 (m, 2H), 4.31-4.37 (m, 2H), 4.63 (ABq, J = 12.5 Hz, AS = 0.15, 2H), 5.09 (d, J = 3.7 Hz, 1H), 5.34 (t, J = 5.5 Hz, 2H), 5.55-5.58 (m, 2H), WO 00/31096 PCT/US99/27828 - 96 5.82 (d, J = 6.2 Hz, 1H), 7.12-7.18 (m, 1H), 7.18-7.27 (m, 5H), 7.34-7.39 (m, 3H), 7.41-7.46 (m, 3H), 7.54 (d, J = 1.8 Hz, 1H), 9.07 (s, 1H); IR (KBr) 3410, 3080, 3030, 2920, 2850, 1735, 1590, 1530, 1450, 1425, 1375, 1310, 1250, 1220, 1145, 1070, 1030, 750, and 700 cm'; mass spectrum [(-) ESI], m/z 758 (M - H); Anal. Calcd. for 5 C,37H 4 2C1NO14 1.0 H20: C, 57.11; H, 5.70; N, 1.80, Found: C, 57.30; H, 5.52; N, 1.77. Example 83 N- f 5-[(4'.6'-O-Benzvlidene-B-D-maltosyl)-oxy-methyll-2-chloro-phenyl l 10 methanesulfonamide step 1

N-{

5

-[(

2

,

2

',

3

,

3

',

4 ',6,6'-Hepta-O-acetyl-p-D-maltosyl)-oxy-methyl].-2-chloro phenyl}-methanesulfonamide To a stirred solution of NaH (0.0467 g, 1.17 mmol) and CH 2 C1 2 (10 mL) at rt 15 was added 2-chloro-5-(hepta-O-acetyl-p-D-maltosyl-oxymethyl)-phenylamine (0.755 mg, 0.973 mmol). After 10 min., MsC1 (0.0906 mL, 1.17 mmol) was added to this solution dropwise, and the reaction was stirred at rt for 18 h. Another 2.4 eq. MsCl added and continued stirring at rt for 144 h. Since reaction was only about 25% complete, it was refluxed for 24 h. Then another 2.4 eq. MsC1 added and continued 20 refluxing for 120 h. The resulting solution was concentrated and then diluted with EtOAc (200 mL). This layer was washed with 1N HC1 (20 mL), sat. NaHCO 3 (20 mL), and brine (20 mL) and then dried (MgSO 4 ). After concentration, the oilly residue was purified by flash chromatography (10:90 to 60:40 acetone:hexane gradient) to afford the product (0.423 g, 51%) as a white foam, mp >73 oC 25 (decomp.); 'H NMR (DMSO-d) 6 1.93 (d, J = 1.8 Hz, 3H), 1.94 (d, J = 1.8 Hz, 3H), 1.95 (d, J = 1.5 Hz, 3H), 1.97 (d, J = 0.9 Hz, 6H), 2.01 (d, J = 1.5 Hz, 3H), 2.08 (d, J = 1.5 Hz, 3H), 3.02 (d, J = 1.3 Hz, 3H), 3.90-4.04 (m, 4H), 4.11-4.23 (m, 2H), 4.38 (d, J = 11.6 Hz, 1H), 4.56 (d, J = 12.7 Hz, 1H), 4.68-4.77 (m, 2H), 4.82-4.89 (m, 2H), 4.97 (t, J = 9.7 Hz, 1H), 5.20 (t, J = 9.4 Hz, 1H), 5.27 (d, J = 3.1 Hz, 1H), 5.27 30 5.34 (m, 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.35 (s, 1H), 7.50 (dd, J = 1.5, 8.3 Hz, 1H), 9.47 (s, 1H); IR (KBr) 3480, 3260, 3010, 2950, 1755, 1590, 1495, 1420, 1375, 1355, 1230, 1140, 1045, 975, 900, and 755 cm'; mass spectrum [(+) FAB], m/z 854 (M + WO 00/31096 PCT/US99/27828 - 97 H)+, 876 (M + Na)', Anal. Calcd. for C 34 H4 4 C1NOOS - 1.25 H 2 0: C, 46.58; H, 5.35; N, 1.60, Found: C, 46.22; H, 4.93; N, 1.49. step 2 5 N-{5-[(P-D-Maltosyl)-oxy-methyl]-2-chloro-phenyl}-methanesulfonamide sodium salt The title compound was prepared as a white solid (0.310 g, 71%) from N-{5 [(2,2',3,3',4',6,6'-hepta-O-acetyl-p3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl} methanesulfonamide using 1.3 eq. 25 weight % NaOMe in MeOH (because of 10 sulfonamide acidity) and a procedure similar to step 4 of Example 1, mp >189 oC (decomp.); 'H NMR (DMSO-d 6 ) 8 2.54 (s, 3H), 3.05 (t, J = 8.1 Hz, 2H), 3.16 (s, 1H), 3.18-3.24 (m, 2H), 3.27-3.42 (m, 2H), 3.42-3.51 (m, 2H), 3.53-3.63 (m, 2H), 3.72 (d, J = 11.2 Hz, 1H), 4.24 (d, J = 7.7 Hz, 1H), 4.44-4.54 (bs, 1H), 4.50 (ABq, J = 11.6 Hz, A6 = 0.24, 2H), 4.54-4.60 (bs, 1H), 4.80-4.93 (bs, 2H), 5.01 (d, J = 3.7 Hz, 1H), 15 5.09-5.18 (bs, 1H), 5.27-5.55 (bs, 2H), 6.47 (dd, J = 2.0, 7.9 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 7.19 (d, J = 2.0 Hz, 1H); IR (KBr) 3410, 2920, 1630, 1590, 1475, 1420, 1375, 1310, 1215, 1140, 1110, 1075, and 1020 cm"'; mass spectrum [(+) FAB], m/z 582 (M + Na)*, Anal. Calcd. for C 2 0

H

29 C1NO1 3 S - Na. 3.5 H20: C, 37.24; H, 5.63; N, 2.17, Found: C, 37.00; H, 5.10; N, 2.13. 20 step 3 N-{5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl} methanesulfonamide The title compound was prepared as a white solid (0.198 g, 55%) from N-{5 25 [(p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl }-methanesulfonamide sodium salt using a procedure similar to Example 24, mp >93 oC (decomp.); 'H NMR (DMSO d6) 8 3.05 (s, 3H), 3.07-3.14 (m, 1H), 32.6-3.42 (m, 4H), 3.42-3.48 (m, 1H), 3.50 3.59 (m, 2H), 3.63-3.75 (m, 3H), 4.11 (d, J = 5.4 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.66 (t, J = 6.6 Hz, 1H), 4.71 (ABq, J = 12.7 Hz, A6 = 0.19, 2H), 5.14 (d, J = 3.7 Hz, 30 1H11), 5.29 (t, J = 4.2 Hz, 2H), 5.51 (d, J = 3.1 Hz, 1H), 5.57 (s, 1H1), 5.63 (d,- J = 6.6 Hz, 1H), 7.30 (dd, J = 1.8, 8.1 Hz, 1H1), 7.34-7.39 (m, 3H), 7.42-7.47 (m, 3H), 7.49 (d, J = 8.1 Hz, 1H1), 9.44 (s, 1H); IR (KBr) 3410, 2910, 2840, 1630, 1590, 1495, WO 00/31096 PCT/US99/27828 - 98 1445, 1385, 1345, 1235, 1160, 1070, 1025, 990, and 755 cm'; mass spectrum [(-) FAB], m/z 646 (M - H); Anal. Calcd. for C 27

H

3 4 C1N0 13 S - 2.0 H 2 0: C, 47.40; H, 5.60; N, 2.05, Found: C, 47.09; H, 4.99; N, 1.98. 5 Example 84 N-{ 5-[(6-O-Benzovl-4'.6'-O-benzylidene-O-D-maltosyl)-oxy-methyl]-2-cvano phenvyl }-acetamide step 1 a-Bromo-2-nitro-p-tolunitrile 10 A stirred mixture containing 4-methyl-2-nitrobenzonitrile (2.04 g, 12.6 mmol), N-bromosuccinimide (2.24 g, 12.6 mmol) and azobisisobutyronitrile (0.103 g, 0.630 mmol) in CC1 4 (50 mL) was irradiated with a 300 watt flood light for 2 h. The reaction was diluted with CH 2 C1 2 (50 ml), filtered and concentrated. Purification by flash chromatography (35 and 40% ether/pet, ether gradient) gave 1.44 g (47%) of 15 the title compound as a yellow oil. 'H NMR (DMSO-d) 8 4.90 (s, 2 H), 8.05 (dd, J = 8.0, 1.5 Hz, 1 H), 8.18 (d, J = 8.0, 1 H), 8.52 (s, 1 H). step 2 cx-Hydroxy-2-nitro-p-tolunitrile 20 A stirred solution containing c-bromo-2-nitro-p-tolunitrile (1.228 g, 5.095 mmol) and sodium formate (0.8664 g, 12.74 mmol) in ethanol:water (4:1, 25 mL) was refluxed for 2 h. The reaction was cooled to room temperature, diluted with 20%

CH

2 Cl/EtOAc, washed with H20 (3x), dried (MgSO 4 ) and concentrated. Purification by flash chromatography (1,2 and 3% MeOH/CHC13 gradient) gave 0.695 g (77%) of 25 the title compound as a white solid. 'H NMR (DMSO-d) 8 4.71 (d, 2 H), 5.75 (t, 1 H), 7.89 (dd, J = 7.9 Hz, 1 H), 8.14 (d, J = 7.9 Hz, 1 H), 8.32 (s, 1 H). step 3 5-[(Hepta-O-acetyl--D-maltosyl)-oxy-methyl]-2-cyano- 1-nitrobenzene 30 At ambient temperature, to a stirred solution of acetobromomaltose (2.39 g, 3.41 mmol), a-hydroxy-2-nitro-p-tolunitrile (0.789 g, 4.43 mmol) and HgBr 2 (1.60 g, 4.43 mmol) in freshly distilled CH 3 CN (34 mL) was added in one portion Hg(CN), WO 00/31096 PCT/US99/27828 - 99 (1.12 g, 4.43 g, mmol). After 16 h, brine (50 mL) was added and the mixture was extracted with 10% CH 2

CJ

2 /EtOAc. The combined organic extracts were washed with brine (3x), dried (MgSO4) and concentrated. Purification by flash chromatography (1,2 and 3% MeOH/CHCl 3 gradient) gave 1.941 g (71%) of the title 5 compound as a foam. An analytical sample was obtained by cyrstallization from EtOAc/Hexane followed by recyrstallization from EtOH to give a colorless solid, mp 155 - 157 oC; 'H NMR (DMSO-d) 6 1.93 (s, 3 H), 1.94 (s, 3 H), 1.97 (s, 3 H), 1.99 (s, 3 H), 2.01 (s, 3 H), 2.06 (s, 3 H), 3.93 - 4.01 (m, 4 H), 4.36 (d, J = 11.0 Hz, 1 H), 4.77 (dd, J = 9.6, 8.0 Hz, 1 H), 4.83 - 4.88 (m, 2 H), 4.93 - 5.00 (m, 3 H), 5.21 (dd, J 10 = 10.3, 9.7 Hz, 1 H), 5.27 (d, J = 3.7 Hz, 1 H), 5.30 - 5.34 (m, 1 H), 7.84 (dd, J = 7.9, 1.5 Hz, 1 H), 8.18 (d, J = 7.9 Hz, 1 H), 8.27 (s, 1 H). IR (KBr) 3450, 2950, 2225, 1750, 1225 and 1050 cm

-

'. mass spectrum [(+) FAB] m/z 797 (M + H)+. Anal. Calcd. for C 3 4 H4oN00: C, 51.26; H, 5.06; N, 3.52. Found: C, 51.06; H, 5.02; N, 3.31. 15 step 4 5-[(Hepta-O-acetyl-p-maltosyl)-oxy-methyl]-2-cyano-phenylamine A stirred mixture containing 5-[(hepta-O-acetyl-0-D-maltosyl)-oxy-methyl]-2 cyano-1-nitrobenzene (1.491 g, 1.872 mmol) iron powder (0.3658 g, 6.550 mmol) and glacial acetic acid (7 mL) in 2-propanol (7 mL) was heated at 75'C for 2 h. To 20 the reaction was added activated charcoal and the hot solution was filtered through a sulka ploc pad, rinsing with EtOAc. The filtrate was washed with H 2 0 (3x), with sat. aq. NaHCO 3 (3x), dried (Na 2

SO

4 ) and concentrated. Purification by flash chromatography (1,2 and 3% MeOH/CHC1 3 gradient) gave 1.04 g (72%) of the title compound. 'H NMR (DMSO-d) 6 1.94 (s, 3 H), 1.95 (s, 3 H), 1.96 (s, 3 H), 1.98 (s, 25 6 H), 2.02 (s, 3 H), 2.09 (s, 3 H), 3.95 - 4.02 (m, 4 H), 4.14 - 4.22 (m, 2 H), 4.36 4.40 (m, 1 H), 4.56 (ABq, J = 13.2 Hz, A6 = 0.09, 2 H), 4.72 (dd, J = 9.4, 8.2 Hz, 1 H), 4.98 (t, J = 9.7 Hz, 1 H), 5.19 - 5.37 (m, 3 H), 6.06 (s, 1 H), 6.49 (dd, J = 8.1, 1.0 Hz, 1 H), 6.66 (s, 1 H), 7.36 (d, J = 8.1 Hz, 1 H). mass spectrum [(+)FAB], m/z 767 (M + H)' . 30 WO 00/31096 PCT/US99/27828 - 100 step 5 N-{5-[(Hepta-O-acetyl-p-D-maltosyl)-oxy-methyl]-2-cyano-phenyl}-acetamide At ambient temperature, to a solution of 5-[(hepta-O-acetyl-p3-maltosyl)-oxy methyl]-2-cyano-phenylamine (0.280 g, 0.365 mmol) in CH 2 C0, (3.6 mL) was added 5 60% NaH/mineral oil (14.6 mg, 0.365 mmol) and the reaction was stirred for 0.5 h. To the reaction was added acetyl chloride (31.3 pL, 0.438 mmol) and the reaction was stirred for 16 h. The reaction was quenched with sat. aq. NaHCO 3 (25 mL) and extracted with EtOAc. The combined organic extracts were dried (Na 2 SO4) and concentrated. Purification by flash chromatography (1,2 and 3% MeOH/CHC1 3 10 gradient) gave 0.249 g (84%) of the title compound. An analytical sample was obtained by cyrstallization from EtOAc/Hexane to give a colorless solid, mp 85 95C; 'H NMR (DMSO-d) a 1.93 (s, 3 H), 1.94 (s, 3 H), 1.95 (s, 3 H), 1.97 (s, 6 H), 2.01 (s, 3 H), 2.07 (s, 3 H), 2.08 (s, 3 H), 3.92 - 4.01 (m, 4 H), 4.13 - 4.21 (m, 2 H), 4.37 (dd, J = 12.0, 2.1 Hz, 1 H), 4.73 (ABq, J = 13.8 Hz, AS = 0.07, 2 H), 4.73 (dd, J 15 = 9.5, 8.0 Hz, 1 H), 4.84 -4.89 (m, 2 H), 4.97 (t, J = 9.8 Hz, 1 H), 5.21 (dd, J = 10.3, 9.7 Hz, 1 H), 5.27 - 5.33 (m, 2 H), 7.21 (dd, J = 8.0, 1.4 Hz, 1 H), 7.48 (s, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 10.15 (s, 1 H). IR (KBr) 3400, 2950, 2225, 1750, 1240 and 1050 cm'. mass spectrum [(+) ESI], m/z 809 (M + H)'. Anal. Calcd. for C 36 H44N 2 0,,: C, 53.47; H, 5.84; N, 3.46. Found: C, 53.55; H, 5.41; N, 3.40. 20 step 6 N-{5-[(P-D-Maltosyl)-oxy-methyl]-2-cyano-phenyl}-acetamide At ambient temperature, to a stirred solution of N-{2-cyano-[5 (2,2',3,3',4',6,6'-hepta-O-acetyl-p-D-maltosyl)-oxy-methyl]-phenyl }-acetamide (2.31 25 g, 2.86 mmol) in MeOH (70 mL) was added in one portion potassium cyanide (92.9 mg, 1.43 mmol). After 3 h, the reactions was concentrated in vacuo. Purification by preparative HPLC (C18, 20% CH 3

CN:H

2 0) and gave 1.18 g (80%) of the title compound; 'H NMR (DMSO-d) a 2.08 (s, 3H), 3.03-3.17 (m, 2H), 3.20-3.49 (m, 7H), 3.50-3.64 (m, 2H), 3.71-3.75 (m, 1H), 4.31 (d, J = 7.6 Hz, 1H), 4.51-4.55 (m, 30 2H), 4.64-4.78 (m, 3H), 4.88-5.00 (m, 2H), 5.02 (d, J = 3.7 Hz, 1H), 5.29-5.53 (m, 3H), 7.38 (dd, J = 8.1, 1.1 Hz, 1H), 7.56 (s, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.80 (s, 1H).

WO 00/31096 PCT/US99/27828 - 101 step 7 N-{5-[(4',6'-O-Benzylidene--D-maltosyl)-oxy-methyl]-2-cyano-phenyl} acetamide 5 The title compound was prepared as a solid (0.682 g, 57%) from N-{5-[(P3-D maltosyl)-oxy-methyl]-2-cyano-phenyl}-acetamide using a procedure similar to Example 24; 'H NMR (DMSO-d 6 ) 8 2.09 (s, 3H), 3.13-3.16 (m, 2H), 3.35-3.73 (m, 9H), 4.12-4.13 (m, 1H14), 4.34 (d, J = 7.8 Hz, 1H), 4.65-4.70 (m, 2H), 4.91 (d, J = 13.6 Hz, 1H), 5.15 (d, J = 3.8 Hz, 1H), 5.32 (m, 2H), 5.55-5.58 (m, 3H), 7.36-7.47 (m, 10 6H), 7.56 (s, 1H), 7.78 (d, J = 8.2 Hz, 1H), 10.17 (s, 1H). step 8 N-{5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-cyano phenyl}-acetamide 15 The title compound was prepared as a white solid (0.173 g, 49%) from N-{5 [(4',6'-O-benzylidene-0-D-maltosyl)-oxy-methyl]-2-cyano-phenyl }-acetamide using a procedure similar to Example 2, mp 122-129 oC; 'H NMR (DMSO-d 6 ) a 2.05 (s, 3H), 3.21 (t, 1H), 3.34-3.41 (m, 2H), 3.53-3.64 (m, 4H), 3.71-3.77 (m, 2H), 4.03 (dd, 1H), 4.34 (dd, J = 12.2, 4.9 Hz, 1H), 4.42 (d, J = 7.7 Hz, 1H), 4.59 (d, 1H), 4.75 20 (ABq, J = 13.7 Hz, A6 = 0.06, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.35 (br. s, 1H), 5.41 (br. s, 1H), 5.52 (s, 1H1), 5.58 (br. s, 1H), 5.82 (br. s, 1H), 7.34-7.37 (m, 4H), 7.40-7.42 (m, 2H), 7.51-7.54 (m, 3H), 7.65 (t, 1H), 7.73 (d, J = 7.9 Hz, 1H1), 7.97-8.00 (m, 2H), 10.13 (s, 1H); IR (KBr) 3400, 2900, 2200, 1710, 1275 and 1065 cm ; mass spectrum [(+) ESI], m/z 724 (M + NH 4 ); Anal. Calcd. for C36 H38N20,13 0.5 H20: C, 60.42; H, 25 5.49 N, 3.91, Found: C, 60.36; H, 5.22; N, 3.91. Example 85 N- { 5-[(6-O-Benzovyl-4'.6'-O-benzvlidene- -D-maltosvl)-oxy-methyll-2-methyl phenylv }-acetamide 30 The title compound was prepared as a colorless solid (1.30 g, 60%) from N { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2-methyl-phenyl }-acetamide using a procedure similar to Example 2, mp 193-198 'C; 'H NMR (DMSO-d,) 6 2.00 WO 00/31096 PCT/US99/27828 - 102 (s, 3H), 2.15 (s, 3H), 3.17 (t, J = 8.4 Hz, 1H), 3.34-3.40 (m, 2H), 3.48-3.62 (m, 4H), 3.69-3.77 (m, 2H), 4.06 (dd, 1H), 4.33-4.38 (m, 2H), 4.60 (ABq, J = 11.9 Hz, A = 0.08, 2H), 4.61 (d, J = 10.5 Hz, 1H), 5.14 (d, J = 4.0 Hz, 1H), 5.33 (br. s, 2H), 5.52 (s, 1H), 5.56 (br. s, 1H), 5.79 (br. s, 1H), 7.06 (dd, 1H), 7.11 (d, J = 7.9 Hz, 1H), 5 7.34-7.37 (m, 4H), 7.40-7.43 (m, 2H), 7.51-7.55 (m, 2H), 7.63-7.68 (m, 1H), 7.99 8.01 (m, 2H), 9.26 (s, 1H); IR (KBr) 3250, 2900, 1725, 1650, 1275 and 1070 cm'; mass spectrum [(+) ESI], m/z 696 (M + H)'; Anal. Calcd. for C 36 H4 1

NO

3 : C, 62.15; H, 5.94; N, 2.01, Found: C, 62.20; H, 6.02; N, 2.04. 10 Example 86 6-[-6-(4-Chloro-3-nitro-benzvlsulfanyl)-4,5-dihydroxy-2-hydroxvmethyl-tetrahydro pyran-3-yloxy]-2-phenvl-hexahydro-pyrano[3,2-d] [1,31 dioxine-7.8-diol step 1 (4-Chloro-3-nitro-benzyl) -hepta-O-acetyl- 1-thio-3-D-maltoside 15 To a stirred solution of hepta-O-acetyl-1-thio-p3-maltose (2.0 g, 3.065 mmol) in acetone (20 ml) were added 4-chloro-3-nitrobenzyl bromide (0.844 mg, 3.37 mmol) and a solution of potassium carbonate (0.423 mg, 3.065 mmol) in water (10 ml). The mixture was boiled under reflux for 30 min, cooled and concentrated. The residue was extracted with dichloromethane, and the combined extracts were washed 20 with water, and brine, dried (MgSO 4 ) and concentrated. Purification by flash chromatography (40%-60% EtOAc/petroleum ether gradient) afforded 1.588 g (63%) of the title compound as a white solid, mp 73-75 oC; 'H NMR (CDC13) 8 1.99 (s, 3 H), 2.00 (s, 3 H), 2.02 (s, 3 H), 2.03 (s, 6 H), 2.11 (s, 3 H), 2.15 (s, 3 H), 3.61 - 3.64 (m, 1 H), 3.80 (d, J = 13.6 Hz, 1H), 3.94 - 4.00 (m, 3 H), 4.08 (dd, J = 12.3, 2.4 Hz, 1 25 H), 4.18 - 4.27 (m, 2 H), 4.36 (d, J = 9.9 Hz, 1H), 4.50 (dd, J = 12.1, 2.6 Hz, 1 H), 4.85 (dd, J = 10.5, 4.0 Hz, 1 H), 4.90 (apparant t, J = 9.9 Hz, 1 H), 5.05 (apparant t, J = 9.9 Hz, 1 H), 5.23 (apparant t, J = 9.2 Hz, 1 H), 5.34 (apparant t, J = 9.7 Hz, 1 H), 5.40 (d, J = 4.0 Hz, 1 H), 7.47 (dd, J = 8.4, 2.0 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 2.0, Hz, 1 H). IR (KBr) 3500, 2950, 1750, 1250 and 1050 cm'", mass 30 spectrum [(+) FAB], m/z 822 (M + H)+, 844 (M + Na)'. Anal. Calcd. for

C

3 3

H

4 0 C1NO 1 S: C, 48.21; H, 4.90; N, 1.70. Found: C, 47.75; H, 4.86; N, 1.65.

WO 00/31096 PCT/US99/27828 - 103 step 2 (4-Chloro-3-nitro-benzyl)- 1-deoxy-1-thio- P-D-maltoside The title compound was prepared as a white solid (0.513 g, 99%) from (4 chloro-3-nitro-benzyl) -hepta-O-acetyl-l1-thio-(3-D-maltoside using a procedure 5 similar to step 4 of Example 1, mp 90-93 oC; 'H NMR (DMSO-d) 8 3.03 - 3.74 (m,, 11 H), 3.80 (d, J = 6.2 Hz, 1 H), 3.86 (d, J = 13.4 Hz, 1 H), 4.01 - 4.08 (m, 2 H), 4.58 (bd, 2 H), 4.98 (bd, 3 H), 5.20 - 5.67 (bs, 3 H), 7.65 - 7.72 (mn, 2 H), 8.03 (d, J = 1.76 Hz, 1 H).IR (KBr) 3400, 2930, 1550, 1300 and1075 cm', mass spectrum [(-) FAB], m/z 526 (M - H).Anal. Calcd. for C 1 9

H

26 C1NO, 2 S * H 2 0: C, 41.80; H, 5.13; N, 2.56. 10 Found: C, 41.35; H, 4.89; N, 2.40. step 3 6-[- 6

-(

4 -Chloro-3-nitro-benzylsulfanyl)-4,5-dihydroxy-2-hydroxymethyl tetrahydro-pyran-3-yloxy]-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8 15 diol The title compound was prepared as a white solid from (4-chloro-3-nitro benzyl)-1-deoxy-1-thio-p3-D-maltoside using a procedure similar to Example 24, mp 120-122 oC; 'H NMR (DMSO-d) 6 3.07-3.24 (m, 2H), 3.24-3.43 (m, 3H), 3.47-3.58 (m, 3H), 3.64-3.75 (m, 3H), 3.95 (ABq, J = 13.4 Hz, A6 = 0.12, 2H), 4.08-4.13 (m, 20 2H), 4.77 (t, J = 5.5 Hz, 1H), 5.12 (d, J = 3.95 Hz, 1 H), 5.28 (d, J = 5.3, Hz, 1H), 5.31 (d, J = 5.3, Hz, 1H), 5.56 (m, 2H), 5.65 (d, J = 6.4, Hz, 1H), 7.35-7.40 (m, 3H), 7.42-7.46 (m, 2H), 7.66-7.71 (m, 2H), 8.04 (d, J = 1.76 Hz, 1H); IR (KBr) 3450, 2930, 1550, 1300 andl075 cm'; mass spectrum [(-) FAB], m/z 614 (M - H); Anal. Calcd. for C,6H 3 0 C1NO1 2 S: C, 49.96; H, 5.1; N,2.24, Found: C, 49.42; H, 4.78; N, 25 2.26. Example 87 (4-Chloro-3-nitro-benzyl) 6-O-benzoyl-4'.6'-O- benzovl-4',.6' ,-O-benzvlidene- 1 thio-f-D-maltoside 30 The title compound was prepared as a white solid from 6-[-6-(4-chloro-3 nitro-benzylsulfanyl)-4,5-dihydroxy-2-hydroxymethyl-tetrahydro-pyran-3-yloxy]-2 phenyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol using a procedure similar to WO 00/31096 PCT/US99/27828 -104 Example 2, mp 105-107 oC; 'H NMR (DMSO) 8 3.17-3.23 (m, 1H), 3.27-3.42 (m, 2H), 3.46-3.51 (m, 1H), 3.53-3.62 (m, 3H), 3.69-3.76 (m, 2H), 3.91 (q, J = 14.1 Hz, 2H), 4.06 (dd, J = 10.3, 4.8 Hz, 1H), 4.28 - 4.34 (m, 2H), 4.62 (d, J = 10.5 Hz, 1H), 5.13 (d, J = 3.7 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.41 (d, J = 6.2 Hz, 1H), 5.53 (s, 5 1H), 5.64 (d, J = 2.9 Hz, 1H), 5.80 (d, J = 6.1 Hz, 1H), 7.31 (m, 3H), 7.40-7.43 (m, 2H), 7.47 (t, J = 5.7 Hz, 2H), 7.59-7.65 (m, 3H), 7.95-7.98 (m, 3H); IR (KBr) 3400, 2930, 1745, 1550, 1255 and1075 cm'; mass spectrum [(+) FAB], m/z 720 (M + H)', 742 (M + Na)+; Anal. Calcd. for C 33

H

34 C1N013S: C, 55.04; H, 4.76; N, 1.95, Found: C, 55.36; H, 4.89; N, 1.91. 10

Claims (24)

1. A compound of formula I having the structure R 7 R1O OXoR R30% OR 2 R 4 0 0 "R R 5 0 X R 6 0 9 I 5 wherein X is O or S; R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon 10 atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with R 8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted with R 8 , and thiazolyl substituted with R 8 ; R 2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 15 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, R12 Rio\ 3RioRo 12 IO -Rio 1/H21 10 R 11 -,r or R lo Rio WO 00/31096 PCT/US99/27828 - 106 R 3 , R 4 , R 5, and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms; 5 R 7 is hydrogen, methyl, or phenyl; R 8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO- , halogen, or-CF3; R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO 2 R 14 , -NHSO 2 R 14 , O0 0 H Ii -U-1 Ro - - R o 0 0 0 -- H N HN H ~~N>K N> RRio R10 R 14 - -NH IP ' - -H') NHR 15 O 0 N R R11 H N ,or R12 N)or R1o -1-NH n 10 R 10 , R 11, and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 15 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3; WO 00/31096 PCT/US99/27828 - 107 R 13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or halogen; 5 R 14 is alkyl of 1-6 carbon atoms; R 15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16 R 16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; p = 0-6; 10 or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein R 2 is hydrogen, acyl of 2-6 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, ,~ R12 Rio Rio R R12 SO -R1o ,R or1CH R13 15 R 3, R 4 , R 5 , and R 6 are each, independently, hydrogen, or acyl of 2-7 carbon atoms; R 9 is hydrogen, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO 2 R 14 , -NHSO 2 R 14 , WO 00/31096 PCT/US99/27828 - 108 R14 -j-NH P ' -- NH NHR 15 +N N +N>k, 0R10 HNHR 1 R R10 11 -I-N 'Ri ,or R12 - o-NHr or a pharmaceutically acceptable salt thereof

3. The compound according to Claim 2, wherein 5 X is O; R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with 10 R 8 , or pyridyl substituted with RS; R 2 is hydrogen, acyl of 2-6 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, R1o R11 0- CH2 n R 10 00 R 1 0 R 11 R10 R1 R 10 R 11 S0 2 0 12 r -R10 2 o r , -R1 1o R13 WO 00/31096 PCT/US99/27828 - 109 R 3 , R

4 , R 5 , and R 6 are each, independently, hydrogen, or acyl of 2-7 carbon atoms; R 7 is hydrogen; R 8 is hydrogen, alkyl of 1-6 carbon atoms, -CN, or halogen; R 13 is hydrogen, alkyl of 1-6 carbon atoms, halogen, or phenyl group, wherein the 5 phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or halogen; R 16 is alkyl of 1-6 carbon atoms, or fluorenyl; or a pharmaceutically acceptable salt thereof. 10 4. The compound of claim 1, which is N-{5-[(6-O-Benzoyl-4',6'-O propylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl } -acetamide or a pharmaceutically acceptable salt thereof;

5. The compound of claim 1, which is N-{5-[(6-O-Benzyl-4',6'-O 15 benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof;

6. The compound of claim 1, which is N-(5-{ [6-O-Benzoyl-4',6'-O-(4 nitro)-benzylidene- P-D-maltosyl]-oxy-methyl }-2-chloro-phenyl)-acetamide or a 20 pharmaceutically acceptable salt thereof;

7. The compound of claim 1, which is N-{5-[(6-O-Benzoyl-4',6'-O isobutylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 25

8. The compound of claim 1, which is N-{5-[(6-O-Benzoyl-4',6'-O-((1R) 2-phenyl-ethylidene)--D-maltosyloxy)-methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 30

9. The compound of claim 1, which is N-{5-{ [6-O-Benzoyl-4',6'-O-((1R) 3-cyanopropylidene)- P-D-maltosyloxy]-methyl }-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -110

10. The compound of claim 1, which is Benzoic acid 6-(3-acetylamino-4 chloro-benzoyloxy)-3-(7,8-dihydroxy-2-pyridin-4-yl-hexahydro-pyrano[3,2-d][1,3] dioxin-6-yloxy)-4,5-dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a 5 pharmaceutically acceptable salt thereof;

11. The compound of claim 1, which is N-{5-[(6-O-Benzoyl-4',6'-O benzylidene-0-D-maltosyl-oxy)-methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 10

12. The compound of claim 1, which is (R)-N-[2-Chloro-5-[[[6-O -(3 trifluoromethylbenzoyl)-4-O-[4,60-(phenyl-methylene)-c-D-glucopyranosyl]-p13-D glucopyranosyl]oxy]-methyl]-phenyl]acetamide or a pharmaceutically acceptable salt thereof; 15

13. The compound of claim 1, which is N-{5-[(4',6'-O-Benzylidene-6-O (2-iodo)-benzoyl--D-maltosyl)-oxy-methyl]-2-chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; 20

14. The compound of claim 1, which is (R)-N-[-2-Chloro-5-[[[6-O (phenylacetyl)-4- O-[4,6-O-(phenylmethylene)-ca-D-glucopyranosyl] - p3-D glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; 25

15. The compound of claim 1, which is N-{5-[(4',6'-O-Benzylidene-6-O phenyl-ethyl-carboxyl-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof;

16. The compound of claim 1, which is 4-Benzoyl-N-{5-[(4',6'-O 30 benzylidene-6-O-(2-iodo)-benzoyl-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl benzamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 111

17. The compound of claim 1, which is N-{5-[(6-O-Benzoyl-4',6'-O benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro-phenyl}-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; 5

18. The compound of claim 1, which is (4-Chloro-3-nitro-benzyl) 6-0 benzoyl-4',6'-O-benzoyl-4',6',-O-benzylidene-l1-thio-p-D-maltoside or a pharma ceutically acceptable salt thereof.

19. The compound of claim 1, which is: 10 a) N- { 2-Chloro-5-[(4',6'-O-ethylidene)--D-maltosyloxymethyl]-phenyl } acetamide or a pharmaceutically acceptable salt thereof; b) (R)-N-[5-[[[6-O-Benzoyl-4-O-(4,6-O-ethylidene-a-D-glucopyranosyl)-p 15 D-glucopyranosyl]oxy]methyl]-2-chlorophenyl]acetamide or a pharmaceutically acceptable salt thereof; c) (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-6-O-benzoyl-4-O-(2,3-di-0 acetyl-4,6- O-ethylidene-ac-D-glucopyranosyl)-p3-D 20 glucopyranosyl]oxy]methyl] phenyl]acetamide or a pharmaceutically acceptable salt thereof; d) N- { 2-Chloro-5-[(4',6'-O-propylidene-p-D-maltosyl)-oxy-methyl] phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 25 e) N-(5- { [4',6'- O-Benzylidene-6- O-(4-toluenesulfonyl)-p3-D-maltosyl] oxy-methyl }-2-chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; 30 f) N-(5- { [2,3,2',3'-Tetra-O-acetyl-4',6'-O-benzylidene-6-O-(4 toluenesulfonyl)-p-D-maltosyl]-oxy-methyl }-2-chloro-phenyl) acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -112 g) N- { 5-[(6-O-Benzyl-4',6'-O-ethylidene-p3-D-maltosyl)-oxy-methyl]-2 chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 5 h) N-(2-Chloro-5- { [4',6'-O-(4-nitro)-benzylidene-p-D-maltosyl]-oxy methyl}-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; i) N- { 2-Chloro-5-[(4',6'-O-(4-chloro)-benzylidene-p-D-maltosyl)-oxy 10 methyl]-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; j) N-{ 5-[(6-O-Benzoyl-4',6'-O-(4-chloro)-benzylidene-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable 15 salt thereof; k) N- { 2-Chloro-5-[(4',6'-O-isobutylidene-p-D-maltosyl)-oxy-methyl] phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 20 1) N- { 5-[(4',6'-O-((1R)-2-Phenyl-ethylidene)-p-D-maltosyloxy)-methyl] 2-chloro-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; m) N- { 2-Chloro-5-[(4',6'-O-((1R)-3-cyano-propylidene)-p-D-maltosyloxy) 25 methyl]-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; n) N- { 2-Chloro-5-[(4',6'-O-((1R)-3-ethoxy-propylidene)-p3-D maltosyloxy)-methyl]-phenyl } -acetamide or a pharmaceutically 30 acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 113 o) N- { 5- { [6-O-Benzoyl-4',6'-O-((1R)-3-ethoxypropylidene)-p-D maltosyloxy]-methyl } -2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 5 p) N-(2-Chloro-5- { [4',6'-O-(4-pyridinemethylidene)-p-D-maltosyl]-oxy methyl }-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; q) N- { 5-[(4',6'-O-Benzylidene-p-D-maltosyloxy)-methyl]-2-chloro 10 phenyl}-acetamide or a pharmaceutically acceptable salt thereof; r) N-{ 5-[(4',6'-O-Benzylidene-2,2',3,3',6-penta-O-acetyl-0-D-maltosyl oxy)-methyl]-2-chloro-phenyl } -acetamide or a pharmaceutically acceptable salt thereof; 15 s) (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-6-O-benzoyl-4-O-[2,3-di-O acetyl-4,6-O-(phenylmethylene)-a-D-glucopyranoysl]-p glucopyranosyl]-oxy]methyl]-phenyl]acetamide or a pharmaceutically acceptable salt thereof; 20 t) (R)-N-[2-Chloro-5-[[[6-O-(5-methoxy-1,5-dioxopentyl)-4-O-[4,6-O (phenylmethylene)-a-D-glucopyranoysl]-P3-D glucopyranosyl]oxy]methyl]-phenyl]acetamide or a pharmaceutically acceptable salt thereof; 25 u) 4-Chloro-3-nitro-benzyl-4',6'-O-benyzlidene-p-D-maltoside or a pharmaceutically acceptable salt thereof; v) 4-Chloro-3-nitro-benzyl-6-O-benzoyl-4',6'-O-benyzlidene-p3-D 30 maltoside or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 114 w) (R)-(4-Chloro-3-nitrophenyl)methyl-2,3-di-O-acetyl-6-O-benzoyl-4-0 [2,3-di-O 0-acetyl-4,6- O-(phenylmethylene)-a-D-glucopyranosyl] - P3-D glucopyranoside or a pharmaceutically acceptable salt thereof; 5 x) Nicotinic acid 6-(4-chloro-3-nitro-benzyloxy)-3-(7,8-dihydroxy-2 phenyl-hexahydro-pyrano [3,2-d] [ 1,3] dioxin-6-yloxy)-4,5-dihydroxy tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 10 y) (R)-(4-Chloro-3-nitrophenyl)methyl 4-[2,3-di-O-acetyl-4,6-O (phenylmethylene)-a-D-glucopyranosyl]-p-D-glucopyranoside 2,3 diacetate 6-(3-pyridinecarboxylate) or a pharmaceutically acceptable salt thereof; 15 z) 4-Methoxy-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d] [ 1,3]dioxin-6-yloxy)-4,5 dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 20 aa) 4-Methoxy-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro benzyloxy)-3-(7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2 d][1,3]dioxin-6-yloxy)-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 25 bb) 4-Chloro-benzoic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-6-yloxy)-4,5 dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 30 cc) 4-Chloro-benzoic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro benzyloxy)-3-(7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2- WO 00/31096 PCT/US99/27828 -115 d][1,3]dioxin-6-yloxy)-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; dd) (R)-N-[2-Chloro-5-[[[6-O -(4-chloro-3-nitrobenzoyl)-4-O-[4,60 5 (phenylmethylene)-a-D-glucopyranosyl]-p-D glucopyranosyl]oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; ee) N-{ 5-[(2,2',3,-Tri-O -Acetyl-6-O -(4-chloro-3-nitrobenzoyl)-4',6'-0 10 (benzylidene)-0-D-maltosyl)-oxymethyl]-2-chloro-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; ff) (R)-N-[2-Chloro-5-[[[6- 0 -(4-cyanobenzoyl)-4-O-[4,60-(phenyl methylene)-a-D-glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl] 15 phenyl]acetamide or a pharmaceutically acceptable salt thereof; gg) (R)-N-[2-Chloro-5-[[[6-O -(4-nitrobenzoyl)-4-O-[4,60-(phenyl methylene)-c-D-glucopyranosyl]-p-D-glucopyranosyl]oxy]methyl] phenyl]acetamide or a pharmaceutically acceptable salt thereof; 20 hh) N- { 5-[(4',6'-O-Benzylidene-6-O-(3-iodo)-benzoyl-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; 25 ii) N- { 5-[(4',6'-O-Benzylidene-6-(4-iodo-benzoyl)-oxy-p3-D-maltosyl)-oxy methyl]-2-chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; jj) (R)-N-[2-Chloro-5-[[[2,3-di-O-acetyl-4-O-[2,3-di-O-acetyl-4,6-O 30 (phenyl-methylene)-a.-D-glucopyranosyl]-6-O-(phenylacetyl)-3-D glucopyranosyl]-oxy]methyl]phenyl]acetamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -116 kk) N- { 5-[(4',6'-O-Benzylidene-6-O-phenyl-propyl-carboxyl-p-D-maltosyl) oxy-methyl]-2-chloro-phenyl } -acetamide or a pharmaceutically acceptable salt thereof; 5 11) Diphenyl-acetic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8 dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3] dioxin-6-yloxy)-4,5 dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 10 mm) Diphenyl-acetic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyl oxy)-3-(7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6 yloxy)-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 15 nn) (3,4-Dimethoxy-phenyl)-acetic acid 6-(3-acetylamino-4-chloro-benzyl oxy)-3-(7,8-dihydroxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6 yloxy)-4,5-dihydroxy-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 20 oo) (3,4-Dimethoxy-phenyl)-acetic acid 4,5-diacetoxy-6-(3-acetylamino-4 chloro-benzyloxy)-3-(7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6-yloxy)-tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 25 pp) Nicotinic acid 6-(3-acetylamino-4-chloro-benzyloxy)-3-(7,8-dihydroxy 2-phenyl-hexahydro-pyrano [3,2-d] [1,3] dioxin-6-yloxy)-4,5-dihydroxy tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; 30 qq) Nicotinic acid 4,5-diacetoxy-6-(3-acetylamino-4-chloro-benzyloxy)-3 (7,8-diacetoxy-2-phenyl-hexahydro-pyrano[3,2-d] [1,3]dioxin-6-yloxy)- WO 00/31096 PCT/US99/27828 -117 tetrahydro-pyran-2-ylmethyl ester or a pharmaceutically acceptable salt thereof; rr) (R)-N-[5-[[[6-O-(4-Benzoylbenzoyl)-4-O-[4,6-O-(phenylmethylene)-a 5 D-glucopyranosyl]-p3-D-glucopyranosyl]oxy]methyl]-2-chlorophenyl] acetamide or a pharmaceutically acceptable salt thereof; ss) N- { 5-[(4',6'- O-Benzylidene- p-maltosyl)-oxy-methyl]-2-methyl phenyl}-acetamide or a pharmaceutically acceptable salt thereof; 10 tt) N-Acetyl- { 5-[(2,2',3,3',6-penta-O-acetyl-4',6'-O-benzylidene-p-D maltosyl)-oxy-methyl]-2-methyl-phenyl } acetamide or a pharmaceutically acceptable salt thereof; 15 uu) N-(5- { [4',6'-O-Benzylidene-6-O-(4-toluenesulfonyl)-p-D-maltosyl] oxy-methyl } -2-methyl-phenyl)-acetamide or a pharmaceutically acceptable salt thereof; vv) N- { 5-[(4',6'-O-Benzylidene-6-O-phenyl--D-maltosyl)-oxy-methyl]-2 20 chloro-phenyl }-acetamide or a pharmaceutically acceptable salt thereof; ww) (R)-N-[2-Chloro-5-[[[4-O-[4',6'-O-(phenylmethylene)-a-D-gluco pyranosyl]-0-D-glucopyranosyl] oxy]methyl] phenyl]-3-pyridine carboxamide or a pharmaceutically acceptable salt thereof; 25 xx) (R)-N-[5-[[[6-O-Benzoyl-4-O-[4',6'-O-(phenylmethylene)-a-D glucopyranosyl]-p-D-glucopyranosyl] oxy]methyl]-2-chlorophenyl]-3 pyridinecarboxamide or a pharmaceutically acceptable salt thereof; 30 yy) Furan-2-carboxylic acid {5-[(4',6'-0-benzylidene-p-D-maltosyl)-oxy methyl]-2-chloro-phenyl }-amide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 -118 zz) Furan-2-carboxylic acid { 5-[(6-O-benzoyl-4',6'-O-benzylidene-p-D maltosyl)-oxy-methyl]-2-chloro-phenyl } -amide or a pharmaceutically acceptable salt thereof; 5 aaa) N- { 2-Chloro-5-[(4',6'-O-benzylidene-p3-D-maltosyl)-oxy-methyl] phenyl}-pent-4-enamide or a pharmaceutically acceptable salt thereof; bbb) N-{2-Chloro-5-[(6-O-benzoyl-4',6'-O-benzilidene-p-D-maltosyl)-oxy 10 methyl]-phenyl}-pent-4-enamide or a pharmaceutically acceptable salt thereof; ccc) 5-(6-O-Benzoyl-4',6'-O-benzylidene-0-D-maltosyl)-oxy-methyl-2 chloro-phenylamine or a pharmaceutically acceptable salt thereof; 15 ddd) (4-Chloro)-benzyl-4',6'-O-benzylidene-p-D-maltoside or a pharmaceutically acceptable salt thereof; eee) Benzoic acid 1-O-(4-chloro)-benzyl-4',6'-O-benzylidene-6-deoxy-p-D 20 malto-6-yl ester or a pharmaceutically acceptable salt thereof; fff) 4-Benzoyl-N- { 5-[(4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2 chloro-phenyl} -benzamide or a pharmaceutically acceptable salt thereof; 25 ggg) 4-Benzoyl-N- {(5-[(6-benzoyl-oxy-4',6'-O-benzylidene-p3-D-maltosyl) oxy-methyl]-2-chloro-phenyl }-benzoic acid amide or a pharmaceutically acceptable salt thereof; 30 hhh) 4-Benzoyl-N- { 5-[(4',6'-O-benzylidene-6-O-(3-iodo-benzoyl)-p-D maltosyl)-oxy-methyl]-2-chloro-phenyl }-benzamide or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 119 iii) 4-Benzoyl-N- { 5-[(4',6'-O-benzylidene-6-(4-iodo-benzoyl)-oxy-p-D maltosyl)-oxy-methyl]-2-chloro-phenyl }-benzoic acid amide or a pharmaceutically acceptable salt thereof; 5 jjj) (1- { 5-[(4',6'-O-Benzylidene-p3-D-maltosyl)-oxy-methyl]-2-chloro phenyl-carbamoyl}ethyl)-carbamic acid 9H-fluoren-9ylmethyl ester or a pharmaceutically acceptable salt thereof; 10 kkk) N-(9H-Fluoren-9ylmethoxycarbonyl)-N'- { 5-[(6-O-benzoyl-4',6'-O benzylidene-p3-D-maltosyl)-oxy-methyl]-2-chloro-phenyl}-L alaninamide or a pharmaceutically acceptable salt thereof; 111) N'-{ 5-[(6-O-benzoyl-4',6'-O-benzylidene-pf-D-maltosyl)-oxy-methyl]-2 15 chloro-phenyl}-L-alaninamide or a pharmaceutically acceptable salt thereof; mmm) N-{ 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxymethyl]-2-chloro phenyl}-N-methyl-acetamide or a pharmaceutically acceptable salt 20 thereof; nnn) N-{ 5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxymethyl]-2 chloro-phenyl}-N-methyl-acetamide or a pharmaceutically acceptable salt thereof; 25 ooo) N- { 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; 30 ppp) N- { 5-[(6-O-(3-Benzyl- 1-oxo-propyl)-4',6'-O-benzylidene-p-D maltosyl)-oxy-methyl]-2-chloro-phenyl }-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; WO 00/31096 PCT/US99/27828 - 120 qqq) N- { 5-[(4',6'-O-Benzylidene-p-D-maltosyl)-oxy-methyl]-2-chloro phenyl}-methanesulfonamide or a pharmaceutically acceptable salt thereof; 5 rrr) N- { 5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2 cyano-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; sss) N- { 5-[(6-O-Benzoyl-4',6'-O-benzylidene-p-D-maltosyl)-oxy-methyl]-2 10 methyl-phenyl}-acetamide or a pharmaceutically acceptable salt thereof; ttt) 6-[-6-(4-Chloro-3-nitro-benzylsulfanyl)-4,5-dihydroxy-2-hydroxy methyl-tetrahydro-pyran-3-yloxy]-2-phenyl-hexahydro-pyrano[3,2 15 d][1,3]dioxine-7,8-diol or a pharmaceutically acceptable salt thereof;

20. A method of treating or inhibiting hyperproliferative vascular disorders in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formula I having the structure 7 R O-0R 0 5 2 R30 R4 RO X I 20 wherein X is O or S; R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon 25 atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with WO 00/31096 PCT/US99/27828 - 121 R 8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted with R 8, and thiazolyl substituted with RS; R 2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 5 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, Ri ,,L R o ORoRo 12 O Rio 1 R1 RioRR1 10 1 2R 12 ' 10 R" 02(C H2) 1O x " N , or R1 o Rio R 3 , R 4 , R 5 , and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, 10 benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms; R 7 is hydrogen, methyl, or phenyl; R 8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, 15 -NO 2 , halogen, or-CF3; R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2, halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO 2 R 14 , -NHSO 2 R 1 4 , WO 00/31096 PCT/US99/27828 - 122 N R o1 -R oN R i - 1-N 0\ - N N N- -N SN N/ Rio RRi4 -- NH P-NH NHR 15 H , or R12 Rio -1-NH n R 10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of 5 the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3; R 13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 10 carbon atoms, or halogen; R 14 is alkyl of 1-6 carbon atoms; R 15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16 R 16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; 15 p = 0-6; or a pharmaceutically acceptable salt thereof. WO 00/31096 PCT/US99/27828 - 123

21. A method of treating or inhibiting restenosis in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of formula I having the structure R 7 R1..O R30 OR 2 R 3 0 R 4 0 R X R8 R 5 0 x R 6 0 I 5 wherein X is O or S; R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon 10 atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with R 8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted with R 8 , and thiazolyl substituted with RS; R 2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 15 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, WO 00/31096 PCT/US99/27828 - 124 O x' J'SN , "or R 10 o R 1 1 o 1/ , [o, Rio R1 R 02io2 i R 3, R 4 , R5, and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , 5 haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacy1 of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms; R 7 is hydrogen, methyl, or phenyl; R is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2, halogen, or-CF3; 10 R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2, halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO2R 14 , -NHSO 2 R 14 WO 00/31096 PCT/US99/27828 - 125 RioRo NHRN H R1l 10 H -N H NH 1 ,or R12 R 1 o ,iNI n R 10, R 11, and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of 5 the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF 3 ; R 13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 10 carbon atoms, or halogen; R 14 is alkyl of 1-6 carbon atoms; R 15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16; R 16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; WO 00/31096 PCT/US99/27828 - 126 p = 0-6; or a pharmaceutically acceptable salt thereof.

22. The method according to claim 21, wherein the restenosis results from 5 a vascular angioplasty procedure, vascular reconstructive surgery, or organ or tissue transplantation.

23. A method of inhibiting angiogenesis in a malignant tumor, sarcoma, or neoplastic tissue in a mammal in need thereof, which comprises administering to said 10 mammal an effective amount of a compound of formula I having the structure R 7 R140 R 3 0'!- -- OR 2 R8 R3 R 0 O X"R R 5 0 X R 6 0 I wherein X is O or S; 15 R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with R 8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted 20 with R 8 , and thiazolyl substituted with RS; R 2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, WO 00/31096 PCT/US99/27828 - 127 R 10 R 1 2 1 OO 0 ~ SNj , orROSR1 oUo 0 Ro lOR 11 .S0 2 -"CH2 n R 1° I -- R Rio Rio o 0 0 N) N> ,orN R 3 , R 4 , R 5 , and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , 5 haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms; R 7 is hydrogen, methyl, or phenyl; R 8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2, halogen, or-CF3; 10 R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO 2 R 14 , -NHSO 2 R 14 , WO 00/31096 PCT/US99/27828 - 128 R -R -k R Rio H R10R14 -NH P N -NH 1 NHR 15 H R12 -. ,N, or R1 o -NH n R 10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2, halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of 5 the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3; R 13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 10 carbon atoms, or halogen; R 1 4 is alkyl of 1-6 carbon atoms; R 15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16 R 16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n = 0-3; WO 00/31096 PCT/US99/27828 - 129 p = 0-6; or a pharmaceutically acceptable salt thereof.

24. A pharmaceutical composition which comprises a compound of 5 formula I having the structure R 7 R 3 0 ! OR 2 8 R 4 0 0 0 "R n R 5 0 X R 6 0 R 9 I wherein Xis 0 or S; 10 R 1 is alkyl of 1-6 carbon atoms, haloalkyl of 1-6 carbon atoms, nitroalkyl of 1-6 carbon atoms, cyanoalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, phenyl mono-, di-, or tri-substituted with R 8 , phenylalkyl of 7-10 carbon atoms, wherein the phenyl ring is mono-, di-, or tri-substituted with R 8 , pyridyl substituted with R 8 , furyl substituted with R 8 , thienyl substituted 15 with R 8 , and thiazolyl substituted with R 8 ; R 2 is hydrogen, acyl of 2-6 carbon atoms, haloacyl of 2-6 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2-7 carbon atoms, or trifluoromethylacyl of 3 8 carbon atoms, carboalkoxyacyl of 4-12 carbon atoms, WO 00/31096 PCT/US99/27828 - 130 0 R 10 R 1 2 Rio O Ro R 3) NR R 1 OO 0 R 10 R 11 'z 1 .S0 2 -JCH2, R 10 0 0 0 KN0 N , or N R1o R1o R 3 , R 4, R 5 , and R 6 are each, independently, hydrogen, acyl of 2-7 carbon atoms, benzoyl, wherein the phenyl moiety is mono-, di-, or tri-substituted with R 8 , 5 haloacyl of 2-7 carbon atoms, nitroacyl of 2-7 carbon atoms, cyanoacyl of 2 7 carbon atoms, or trifluoromethylacyl of 3-8 carbon atoms; R 7 is hydrogen, methyl, or phenyl; R 8 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, or-CF3; 10 R 9 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , -NHR 3 , -NR 3 R 3 , -NR 3 R 14 , -NHCO 2 R 14 , -NHSO 2 R 14 ' WO 00/31096 PCT/US99/27828 - 131 1 Rlo ±kR1 R14 -NH P ' - -NH 1 NHR 15 H ,or 1.1 R 10 o -I-NH n R 10 , R 11 , and R 12 , are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, phenyl, -CN, -NO 2 , halogen, -CF 3 , acyl of 2-7 carbon atoms, or benzoyl, wherein the phenyl group or the phenyl moiety of 5 the benzoyl group is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, or -CF3; R 13 is hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, -CN, -NO 2 , halogen, -CF 3 , or phenyl group, wherein the phenyl moiety is optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkoxy of 1-6 10 carbon atoms, or halogen; R 14 is alkyl of 1-6 carbon atoms; R 15 is hydrogen, acyl of 2-7 carbon atoms, benzoyl, or -CO2R16 R 16 is alkyl of 1-6 carbon atoms, benzyl, phenyl, or fluorenyl; n =0-3; 15 p =0-6; or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.