JPH06211776A - Intermediate of cyclic polyamine derivative - Google Patents

Abstract

PURPOSE:To obtain the subject new compound useful for laminating a macrocyclic polyamine having catalytic activity, etc. CONSTITUTION:The objective compound of formula I {R1 is H, formula II[R2 is H, formula III (R4 is H; R5 is COH, tosyl; or R4 and R5 are both phthaloyl); R3 is COH, tosyl; or R2 and R3 are both phthaloyl]; (n), (m) and (p) are each 2-4}, e.g. N<3>-benzyl-N<1>, N<5>-ditosl-3-aza-1,5-pentadiamine. The compound of the formula I can be obtained, through a compound of formula VI, etc., by reaction of a compound of formula IV as the starting material with a compound of formula V in a solvent such as acetonitrile in the presence of an excess of NaHCO3.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a laminated macrocyclic polyamine intermediate for synthesis. The macrocyclic polyamine derivative is a compound that has a biomimetic function, responds sensitively to the type of substrate, and can be used as a catalyst that exhibits self-organizing ability.

[0002]

BACKGROUND OF THE INVENTION Natural polyamines (eg, spermidine, spermine, thermon, thermosvermine) have been attracting attention as intracellular function regulators. Therefore, the present inventors synthesized a long-chain polyamine derivative which is expected to have physiological activities such as intracellular function regulating action. further,
Macrocyclic polyamines and macrocyclic polyamines, which are a type of polyamine, have the ability to take in molecules and metal ions in the center, and macrocyclic polyamines that take in molecules and metal ions exhibit various activities such as catalytic activity. Is known to do. Therefore, the present inventors have synthesized macrocyclic polyamine derivatives [JP-A-2-73063 and 2-1.
17653].

By the way, it is considered that macrocyclic polyamines, like crown ethers, recognize substances depending on the size of the ring. However, the recognition is due to a single ring. Until now, no compound has been known that recognizes a substance by two or more rings. In addition, spatial recognition of substances is also performed by enzymes in the body,
It is thought that this will lead to the provision of new catalysts. Therefore, the present inventors tried to synthesize a compound having a molecular recognition space by stacking macrocyclic polyamines.
However, the conventional macrocyclic polyamine cannot be laminated as it is because of its structure. Then, the objective of this invention is to provide the macrocyclic polyamine derivative which is a synthetic intermediate for providing the laminated compound of macrocyclic polyamine.

[0004]

The present invention includes the following general formulas (I), (II) and (I
II) and compounds represented by (IV).

[0005]

[Chemical 10]

(Wherein R ¹ is a hydrogen atom or
1 is a group represented by the formula 1, R ² is a hydrogen atom or a group represented by the formula 12, R ³ is a CHO group or a Ts group, or R ² and R ³ Represents a Phth group, wherein R ⁴ represents a hydrogen atom, and R ⁵ represents C
HO group or Ts group, or R ⁴ and R ⁵ are Phth
Represents a group, and n, m and p are each independently an integer of 2 to 4. )

[0007]

[Chemical 11]

[0008]

[Chemical 12]

[0009]

[Chemical 13]

[0010]

[Chemical 14]

(In the formula, R ⁶ represents a group represented by the following formula 15 or formula 16 (provided that in the formula of formula 15, n is
Is an integer of 0 to 2, and in the formula of Chemical formula 16, p is 3 or 4. ), R ⁷ represents a hydrogen atom, an Ms group or a Ts group, and M
Is 2 or 3. In the formula of Chemical formula 14, q is an integer of 2 to 4. )

[0012]

[Chemical 15]

[0013]

[Chemical 16]

[0014]

[Chemical 17]

(Wherein R ⁸ represents a hydrogen atom, a Bn group, or a group represented by the formula (18) (where r is an integer of 2 to 4); R ⁹ is a hydrogen atom or B
represents an n group, m is 1 or 2, n1, n2, p1 and p2 are each independently an integer of 1 to 3, x1 and x
2 is each independently 1 or 2, y1 and y2 are each independently 0, 1 or 2, and Z is 0 or 1. )

[0016]

[Chemical 18]

The present invention will be described below according to a scheme. In the present specification, the Ts group is tosyl (SO ₂ C ₆ H ₄
Indicates -CH ₃₎ group, Phth group represents a phthaloyl group, Ms group designates an Mejiru (SO ₂ CH ₃₎ group, Bn group a benzyl (CH ₂ Ph) group. Compounds of general formula (I) (Scheme 1)

[0018]

[Chemical 19]

The compound of the present invention represented by the general formula (I) is
The compound can be synthesized by the synthetic route represented by the scheme 1 of Chemical formula 19. In addition, m, n, p of each compound of Scheme 1
Is synonymous with m, n and p in the general formula (I).

Benzylamine (1) and bromoamide (2) are combined with excess amount of NaH in a solvent such as acetonitrile.
The compound (3) of the present invention can be obtained by reacting in the presence of CO ₃ . This reaction is suitably carried out by stirring the reaction solution under heating, for example, at 50 to 80 ° C. for 50 to 100 hours. Benzylamine (1) is a commercially available compound, and bromoamide (2) is M. Iwata and H. Ku.
zuhara, Bull.chem.Soc.Jpn., 62 , 198 (1989).

Then, the compound (5) of the present invention can be obtained by reacting the compound (3) with the N-phthaloyl compound (4). This reaction is suitably carried out in the presence of excess potassium carbonate in a solvent such as dimethylformamide at room temperature for 3 to 10 days. In addition, N-
The phthaloyl compound (4) is produced by S. Gabriel and J. Weiner,
It can be synthesized by the method described in Ber., 21 , 2669 (1888).

The compound (5) of the present invention can be obtained by reacting the compound (5) with hydrazine hydrate.
This reaction is carried out in a solvent such as dimethylformamide, for example,
It is suitable to carry out heating at 50 to 80 ° C for 1 to 3 days.

The compound (6) can be tosylated with tosyl chloride to obtain the compound (7) of the present invention. The tosylation can be carried out, for example, by reacting the compound (6) with hydrochloric acid in a solvent such as chloroform and then reacting the product with a tosylating agent such as tosyl chloride in a solvent such as pyridine. The reaction with hydrochloric acid can be carried out by heating at 50 to 80 ° C. for 1 to 10 hours, and the reaction with the tosylating agent is suitably carried out by stirring at room temperature for 5 to 24 hours.

The compound (7) can be phthaloylated in the same manner as in the synthesis of the compound (5) to obtain the compound (8) of the present invention. Further, the compound (8) can be reacted with hydrazine in the same manner as in the synthesis of the compound (6) to obtain the compound (9) of the present invention.
Further, the compound (9) can be tosylated to give the compound (10) of the present invention in the same manner as in the synthesis of the compound (7). Compound of general formula (II) (Scheme 2)

[0025]

[Chemical 20]

The compound of the present invention represented by the general formula (II) is
It can be synthesized by the route of Scheme 2 of Chemical formula 20. Incidentally, n in the scheme 2 corresponds to n in the general formula (II),
A case where m is 2 will be described as an example. Tosylamide (1
The compound (13) of the present invention can be obtained by reacting 1) with commercially available 2-bromoethanol (12) (when m is 3, 3-bromo-1-propanol is used).
This reaction can be carried out by stirring in a solvent such as dimethylformamide in the presence of excess potassium carbonate at room temperature for 1 to 5 days. The compound (13) of the present invention can be obtained by reacting the compound (13) with methanesulfonyl chloride. This reaction is carried out in the presence of excess triethylamine in a solvent such as methylene chloride at room temperature for 10 minutes to
It can be performed by stirring for 5 hours.

Tosylamide (15) can be reacted with commercially available 3-bromo-1-propanol (2-bromoethanol is used when m is 2) to obtain the compound (17) of the present invention. . Reaction is compound (13)
Can be performed in the same manner as in the synthesis of. Compound (17)
Is mesylated with methanesulfonyl chloride in the same manner as in the synthesis of compound (14) to give compound (18) of the present invention.
Can be obtained. Tosylamides (11) and (15) are known compounds and are known to M. Iwata and H. Kuzuhara,
Bull.chem.Soc.Jpn., (A) 55 , 2153 (1982): (b) 59 ,
It can be synthesized by the method described in 1031 (1986). Compound of general formula (III) (Scheme 3)

[0028]

[Chemical 21]

The compound represented by the general formula (III) can be synthesized by the scheme 3. In Scheme 3, the general formula (II
The case where q of I) is 3 will be described.

Commercially available benzylamine (1) and commercially available 1,
The compound (19) of the present invention can be obtained by reacting with 3-dibromopropane. This reaction can be performed by stirring in a solvent such as acetone tolyl at 50 to 70 ° C. for 12 to 48 hours in the presence of an excess amount of sodium hydrogen carbonate. Synthesis of compound of general formula (IV) (Schemes 4 to 7) Synthesis of N-monobenzyl cyclic polyamine (Scheme 4)

[0031]

[Chemical formula 22]

As shown in Scheme 4, the compound (A) represented by the general formula (I) and the compound (B) represented by the general formula (II) (provided that X is OMs or OTs), or The compound (C) of the present invention is obtained by reacting with a commercially available dibromo compound (B) (provided that X is Br).
In the compound (C), Z is 0 in the general formula (IV), R ⁸
Corresponds to a compound in which Bn is. The reaction is carried out in the presence of excess potassium carbonate in a solvent such as dimethylformamide at room temperature.
It can be performed by stirring for 1 to 24 hours. Synthesis of N, N'-dibenzyl cyclic polyamine (Scheme
5)

[0033]

[Chemical formula 23]

As shown in Scheme 5, the compound (A) represented by the general formula (I) and the compound (D) represented by the general formula (IV) are reacted in the same manner as in the reaction of the scheme 4. Thus, the compound (E) of the present invention can be obtained. The compound (E) has the formula (IV), Z is 1, and R ⁸
And R ⁹ is Bn. Derivation of cyclic amine by de-N-benzylation (scheme
6)

[0035]

[Chemical formula 24]

As shown in Scheme 6, the compound (F) of the present invention is obtained by catalytically reducing the above compound (C).
Can be obtained. The compound (F) corresponds to the compound of the general formula (IV) in which Z is 0 and R ⁸ is a hydrogen atom. Similarly, by catalytically reducing the above compound (E), the compounds (G) and (H) of the present invention can be obtained. The compound (G) corresponds to a compound in which Z is 1 in the general formula (IV) and R ⁸ and R ⁹ are hydrogen atoms, and the compound (H) is Z in the general formula (IV) and Z is 1. It corresponds to a compound in which one of ^{8 and} R ⁹ is a hydrogen atom and the other is a benzyl group. The catalytic reduction is suitably carried out using hydrogen in a solvent such as acetic acid in the presence of a catalyst such as Pd-C for 50 to 100 hours. N- (ω-bromoalkylation) of cyclic amine (scheme
7)

[0037]

[Chemical 25]

As shown in Scheme 7, the compound (J) of the present invention can be obtained by reacting the above compound (F) with dibromoalkyl (I). The compound (J) corresponds to the compound of the general formula (IV) in which Z is 0 and R ⁸ is a bromoalkylene group [(CH ₂ ) _n Br]. This reaction can be carried out by stirring in a solvent such as acetonitrile at 50 to 70 ° C. for 5 to 30 hours in the presence of an excess amount of sodium hydrogen carbonate.

[0039]

[Usefulness] The compound of the present invention is useful as a synthetic intermediate for a laminated macrocyclic polyamine, which is expected to have unprecedented substrate responsiveness.

EXAMPLES The present invention will be further described below based on examples.

Synthesis of diamide Example 1-1 N ⁴ -benzyl-N ¹ , N ⁷ -ditosyl-4-aza-1,
7-Heptanediamine (3b):

[0041]

[Chemical formula 26]

Benzylamine (Compound 1: 1.2 g) and N-tosyl-3-bromopropylamine (Compound 2b: 7.53 g, 2.3 molar equivalents relative to (1)) were dissolved in acetonitrile (80 ml) to prepare a hydrogen carbonate solution. Sodium (9.41 g, 10 equivalents based on (1)) was mixed, and the mixture was heated with stirring at about 70 ° C. for 70 hours. The reaction solution is cooled, the remaining sodium hydrogen carbonate is filtered off,
The filtrate was concentrated and subjected to silica gel column chromatography (eluting with chloroform: acetone 4: 1 v / v) to give 5.89 (yield 99
%) Of compound 3b was obtained as a viscous liquid. Compound 3b: C ₂₇ H ₃₅ O ₄ N ₃ S ₂ (molecular weight 529.706) Calculated by elemental analysis: C, 61.22; H, 6.66; N, 7.93;
S, 12.11% Found: C, 60.87; H, 6.55; N, 7.67; S, 12.19% IR (KRS) ν 3290 (NH), 1320, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 1 Two

Example 1-2 In the same manner as in Example 1-1, N ³ -benzyl-N ¹ , N
⁵ -Ditosyl-3-aza-1,5-pentanediamine (3a) was obtained by the reaction of Compound 1 with N-tosyl-2-bromoethylamine in 99% yield. Compound 3a: C ₂₅ H ₃₁ O ₄ N ₃ S ₂ (501.654) calculated by elemental analysis: C, 59.85; H, 6.23; N, 8.38; S,
12.78% Found: C, 59.46; H, 6.12; N, 8.12; S, 13.02% IR (KRS) ν 3290 (NH), 1320, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

Chain Extension Example 2-1 N ⁸ -benzyl-N ¹ , N ¹ ; N ¹⁵ , N ¹⁵ -diphthaloyl-
N ^4, N ¹³ - ditosylate 4,8,12-triaza-1,1
5-pentadecanediamine (5c):

[0045]

[Chemical 27]

Dimethylformamide (DMF) (45 ml)
In, the compound 3b (1.76 g) obtained in Example 1-1, N-
(3-Bromopropyl) phthalimide (4b, 3.3g, 3
b) (3 molar equivalents to b) and potassium carbonate (6.9 g, 15 molar equivalents to 3b) were stirred at room temperature for 6 days. The excess potassium carbonate was removed by filtration, the filtrate was concentrated, and the silica gel chromatograph (eluent chloroform: acetone (95: 5 (30
(0 ml) → 9: 1 (300 ml) v / v)), 3.0 g (yield 99%) of Compound 5c was obtained as a viscous liquid. Compound 5c: C ₄₉ H ₅₃ O ₈ N ₅ S ₂ (904.086) calculated by elemental analysis: C, 65.09; H, 5.91; N, 7.75; S,
7.09% Measured value: C, 64.96; H, 5.85; N, 7.74; S, 7.15% IR (KRS) ν 1710, 1771 (C = 0), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

Example 2-2 The compound 3a obtained in Example 1-2 in the same manner as in Example 2-1.
And a 4b, N ⁷ - benzyl ^{-N 1, N 1; N 13} , N 13 - Jifutaroiru -N ^4, N ¹⁰ - ditosylate 4,7,10-triaza 1,13 (5b) is Obtained as a viscous liquid in 99% yield. Compound 5b: C ₄₇ H ₄₉ O ₈ N ₅ S ₂ (876.034) calculated by elemental analysis: C, 64.44; H, 5.64; N, 8.00;
S, 7.32% Measured value: C, 64.52; H, 5.48; N, 8.06; S, 7.33% IR (KRS) ν 1770, 1710 (C = 0), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2 Example 2-3

[0048]

[Chemical 28]

Compound 3b and N- were prepared in the same manner as in Example 2-1.
From (4-bromobutyl) phthalimide (4c) to N ⁹ −
Benzyl-N ¹ , N ¹ ; N ¹⁷ , N ¹⁷ -diphthaloyl-N
⁵ , N ¹³ -ditosyl-5,9,13-triaza-1,1
7-Heptadecanediamine (5d) as a viscous liquid 99
% Yield. Compound _{5d: C 51 H 57 0 8} N 5 S 2 (932.138) Analysis Calculated: C, 65.71; H, 6.16 ; N, 7.51; S,
6.88% Measured value; C, 65.40; H, 5.96; N, 7.26; S, 6.85% IR (KRS) ν 1770, 1710 (C = 0), 1330, 1150 (SO ₂ )
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

Phthalimide → formamide Example 3-1 N ⁸ -benzyl-N ¹ , N ¹⁵ -diformyl-N ⁴ , N ¹² -ditosyl-4,8,12-triaza-1,15-pentadecanediamine (6c):

[0051]

[Chemical 29]

Compound 5c (2.97 g) obtained in Example 2-1 and hydrazine hydrate (3 ml, 20 per 20 ml per 6 c) in DMF (60 ml).
Was heated at 75 ° C. for 2 days. The reaction solution was concentrated under reduced pressure, and chloroform (60 ml) was added. Remove the precipitate,
The filtrate was concentrated and chromatographed on silica gel (eluent chloroform: methanol 93: 7 v / v (300 ml)).
1.74 g (76% yield) of compound 6c was obtained as a viscous liquid. Compound _{6c: C 35 H 49 O 6} N 5 S 2 (699.914) Analysis Calculated: C, 60.06; H, 7.06 ; N, 10.01; S,
9.16% Found: C, 60.22; H, 7.00; N, 10.12; S, 9.02% IR (KRS) ν 3300 (NH), 1670 (C = 0), 1330, 1155
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2 Example 3-2

[0053]

[Chemical 30]

From the compound 5b obtained in Example 2-2 in the same manner as in Example 3-1, N ⁷ -benzyl-N ¹ , N ¹³ -diformyl-N ⁴ , N ¹⁰ -ditosyl-4,7,10-. Triaza-1,13-tridecanediamine (6b) was obtained as a viscous liquid with a yield of 95%. Compound _{6b: C 33 H 45 O 6} N 5 S 2 (671.862) Analysis Calculated: C, 58.99; H, 6.75 ; N, 10.43; S,
9.55% Actual value: C, 58.62; H, 6.73; N, 10.31; S, 9.62% IR (KRS) ν 3300 (NH), 1670 (C = 0), 1330, 1155
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2 Example 3-3

[0055]

[Chemical 31]

The compound 5d obtained in Example 2-3 in the same manner as in Example 3-1 to N ⁹ -benzyl-N ¹ , N ¹⁷ -diformyl-N ⁵ , N ¹³ -ditosyl-5,9,13-. Triaza-1,17-heptadecanediamine (6d) was obtained as a viscous liquid (yield is about 90%: a pure frame fraction in the chromatography was used as an analytical sample.) Compound 6d: C ₃₇ H ₅₃ O ₆ N ₅ S ₂ (727.966) Elemental analysis calculated value: C, 61.04; H, 7.34; N, 9.62; S,
8.81% Found: C, 61.09; H, 7.35; N, 9.38; S, 8.54% IR (KRS) ν 3300 (NH), 1670 (C = 0), 1320, 1155
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2

Formamide → tosylamide Example 4-1 N ⁸ -benzyl-N ¹ , N ⁴ , N ¹² , N ¹⁵ -tetratosyl-4,8,12-triaza-1,15-pentadecanediamine (7c):

[0058]

[Chemical 32]

The compound 6c (1.70 g) obtained in Example 3-1 was dissolved in chloroform (5 ml), 6N-hydrochloric acid (10 ml) was added, and the mixture was heated and stirred at 70 ° C. for 4 hours. The reaction solution was concentrated under reduced pressure as it was, and pyridine (60 ml) and tosyl chloride (1:16) were added to the residue.
2.5 molar equivalents (g, 6c) were added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, a small amount of chloroform was added to the residue to dissolve it, and the mixture was dissolved in silica gel column chromatography (eluent chloroform: acetone 9: 1 (300 ml) → 4: 1 (300 ml).
v / v) gave 1.27 g (yield 55%) of compound 7c (viscous liquid). Compound _{7c: C 47 H 61 O 8} N 5 S 4 (952.262) Analysis Calculated: C, 59.28; H, 6.46 ; N, 7.36; S,
13.47% Found: C, 58.95; H, 6.43; N, 7.27; S, 13.45% IR (KRS) ν 3290 (NH), 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2 Example 4-2

[0060]

[Chemical 33]

From compounds 6b and 6d obtained in Examples 3-2 and 3-3 in the same manner as in Example 4-1, N ⁷ -benzyl-N ¹ , N ⁴ , N ¹⁰ , N ¹³ -tetratosyl-4 was prepared. , 7,
10-triaza-1,13-tridecanediamine (7
b), and N ⁹ - benzyl ^{-N 1, N 5, N 13} , N 17 -
Tetratosyl-5,9,13-triaza-1,17-heptadecanediamine (7d) was obtained as a viscous liquid in 51% and 69% yields, respectively. Compound 7b: IR (KRS) ν 3290 (NH), 1320, 1155
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2 Compound 7d: C ₄₉ H ₆₅ O ₈ N ₅ S ₄ (980.314) Calculated by elemental analysis: C, 60.03; H, 6.68; N, 7.15; S ，
13.08% Found: C, 59.77; H, 6.56; N, 6.92; S, 13.21% IR (KRS) ν 3260 (NH), 1320, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2 Example 4-3

[0062]

[Chemical 34]

Compound 7d obtained in Examples 4-2 and 4-1
And 7c, it is possible to further extend the chain through three processes similar to the chain elongation, formamidation and tosylamidation of Examples 2-1, 3-1 and 4-1.
First, the compound 7b in the same manner as the compound 3b in Example 2-1
Reaction with compound 4b yielded N ¹¹ -benzyl-N ¹ , N ¹ ; N ²¹ ,
N ²¹ - Jifutaroiru ^{-N 4, N 8, N 14} , N 18 - Tetoratoshiru -4,8,11,14,18- pentaaza -1,21
-Heneicosandiamine (8b) as an amorphous powder,
It was given in a yield of 91%. Compound 8b: C ₆₇ H ₇₅ O ₁₂ N ₇ S ₄ (1298.59) calculated by elemental analysis: C, 61.97; H, 5.82; N, 7.55; S,
9.88% Measured value: C, 61.88; H, 5.80; N, 7.36; S, 9.82% IR (KRS) ν 1770, 1710 (C = 0), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

The above compound 8b was then treated in the same manner as compound 5c of Example 3-1 to give the corresponding formamide N ¹¹ -benzyl-N ¹ , N ²¹ -diformyl-N ⁴ , N ⁸ ,
N ¹⁴ , N ¹⁸ -Tetratosyl-4,8,11,14,18
-Pentaaza-1,21-heneicosandiamine (9
b) was obtained as a viscous liquid in a yield of 88%. Compound _{9b: C 53 H 71 O 10} N 7 S 4 (1094.418) Analysis Calculated: C, 58.16; H, 6.54 ; N, 8.96; S, 1
1.72% Found: C, 57.91; H, 6.34; N, 8.84; S, 11.71% IR (KRS) ν 3300 (NH), 1670 (C = 0), 1330, 1150
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2

Then, the compound 9b was treated in the same manner as the compound 6c of Example 4-1 to give the corresponding tosyl acid derivative N ¹¹ -benzyl-N ¹ , N ⁴ , N ⁸ , N ¹⁴ , N ¹⁸ , N.
²¹ -Hexatosyl-4,8,11,14,18-pentaaza-1,21-heneicosanediamine (10b) was provided as an amorphous powder in 93% yield. Compound 10b: C ₆₅ H ₈₃ O ₁₂ N ₇ S ₆ (1346.766) calculated by elemental analysis: C, 57.97; H, 6.21; N, 7.28; S, 1
4.29% Found: C, 58.07; H, 6.22; N, 6.93; S, 11.59% IR (KBr) ν 3290 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2 Example 4-4

[0066]

[Chemical 35]

Similarly to the compound 3b of Example 2-1, the compound 7c obtained in Example 4-1 was reacted with the compound 4c to give N ^12.
- benzyl ^{-N 1, N 1, N 23} , N 23 - Jifutaroiru -N ^{4,
N 8, N 16, N 20} - Tetoratoshiru -4,8,12,16,
20-Pentaaza-1,23-tricosanediamine (8
c) was provided as a viscous liquid in a yield of 85%. Compound _{8c: C 69 H 79 O 12} N 7 S 4 (1326.642) Analysis Calculated: C, 62.47; H, 6.00 ; N, 7.39; S,
9.67% Found: C, 62.30; H, 6.15; N, 7.35; S, 9.45% IR (KRS) ν 1770, 1710 (C = 0), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

Then, the compound 8c was treated in the same manner as the compound 5c of Example 3-1 to give N ¹² -benzyl-N ¹ , N ²³ -diformyl-N ⁴ , N ⁸ ,
N ¹⁶ , N ²⁰ -Tetratosyl-4,8,12,16,20
-Pentaaza-1,23-tricosandiamine (9c)
Was obtained as a viscous liquid in 90% yield. Compound 9c: C ₅₅ H ₇₅ O ₁₀ N ₇ S ₄ (1122.47) calculated by elemental analysis: C, 58.85; H, 6.74; N, 8.74; S,
11.43% Measured value: C, 58.57; H, 6.70; N, 8.92; S, 11.05% IR (KRS) ν 3300 (NH), 1670 (C = 0), 1300, 1142
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2

[0069] Then, when treated in the same manner as the compound 6c of Example 4-1 The above compound 9c, N ¹² is Toshiruashido body - benzyl ^{-N 1, N 4, N 8} , N 16, N 20, N 23 - Hexatosyl-4,8,12,16,20-pentaaza-
1,23-Tricosanediamine (10c) was obtained as an amorphous powder in a yield of 95%. Compound _{10c: C 67 H 87 O 12} N 7 S 6 (1374.818) Analysis Calculated: C, 58.53; H, 6.38 ; N, 7.13; S,
13.99% Found: C, 58.57; H, 6.16; N, 7.29; S, 13.67% IR (KRS) ν 3290 (NH), 1325, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2 Example 4-5

[0070]

[Chemical 36]

Similarly to the compound 3b of Example 2-1, the compound 7c obtained in Example 4-1 was reacted with the compound 4c to give N.sub.2.
¹³ -benzyl-N ¹ , N ¹ , N ²⁵ , N ²⁵ -diphthaloyl-N
^{5, N 9, N 17,} N 21 - Tetoratoshiru -5,9,13,1
7,21-Pentaaza-1,25-pentacosanediamine (8d) was provided as an amorphous powder in 95% yield. Compound 8d: C ₇₁ H ₈₃ O ₁₂ N ₇ S ₄ (1354.694) calculated by elemental analysis: C, 62.95; H, 6.18; N, 7.24; S,
9.47% Actual value: C, 62.71; H, 6.10; N, 7.17; S, 9.60% IR (KBr) ν 1770, 1710 (C = 0), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

Then, the above compound 8d was treated in the same manner as the compound 5c of Example 3-1 to give N ¹³ -benzyl-N ¹ , N ²⁵ -diformyl-N ⁵ , N ⁹ ,
N ¹⁷ , N ²¹ -tetratosyl-5,9,13,17,21
-Pentaaza-1,25-pentacosanediamine (9
d) was given as an amorphous powder. (The pure sample in the column chromatography was used as the analytical sample.) Compound 9d: C ₅₇ H ₇₉ O ₁₀ N ₇ S ₄ (1150.522) Calculated by elemental analysis: C, 59.39; H, 6.88; N, 8.38; S ，
11.13% Found: C, 59.39; H, 6.88; N, 8.38; S, 11.13% IR (KBr) ν 3400 (NH), 1670 (C = 0), 1330, 1150
(SO ₂ ) cm ⁻¹ NMR (CDCl ₃ ) Tables 1 and 2

Then, the compound 9d was treated in the same manner as the compound 6c of Example 4-1 to give N ¹³ -benzyl-N ¹ , N ⁵ , N ⁹ , N ¹⁷ , N ²¹ , N ^25- which is a tosyl acid compound. Hexatosyl-5,9,13,17,21-pentaaza-
1,25-Pentacosanediamine (10d) was provided as an amorphous powder in a yield of 77% (of calculated value based on 8d). Compound _{10d: C 69 H 91 O 12} N 7 S 6 (1402.87) Analysis Calculated: C, 59.07; H, 6.54 ; N, 6.99; S,
13.71% Found: C, 58.97; H, 6.44; N, 6.89; S, 13.76% IR (KRS) ν 3290 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Tables 1 and 2

[0074]

[Table 1]

[0075]

[Table 2]

[0076]

[Chemical 75] Tosyl acid → diol Example 5-1

[0077]

[Chemical 37]

N ⁴ , N ⁹ -ditosyl-4,9-diaza-
1,12-Dodecanediol (17b): DMF (60 ml)
Medium, N, N'-ditosyl-1,4-butanediamine (15
b; 1.623 g), 3-bromo-1-propanol (16: 1.308
g, 15b 2.3 molar equivalents), potassium carbonate (5.66g,
15 mol) was mixed with 15b and stirred at room temperature for 2 days. Pass the reaction solution through Celite, concentrate the solution, and concentrate on silica gel column chromatography (eluent chloroform: acetone 8: 2 (300 ml) → chloroform: methanol).
9: 1 (300 ml) v / v), and the 17b fraction was collected and concentrated. Recrystallization of the residue from methanol gives 1.83 g.
Compound 17b (yield 87%) was obtained. Compound 17b: C ₂₄ H ₃₆ O ₆ N ₂ S ₂ (512.676) mp 126 to 127 ° C. (recrystallized from methanol) Calculated by elemental analysis: C, 56.22; H, 7.08; N, 5.47; S,
12.51% Measured value: C, 56.20; H, 7.09; N, 5.38; S, 12.36% IR (KRS → KBr) ν 3550 (OH), 1330, 1150 (SO ₂ ).
cm ^-1 NMR (CDCl ₃ ) Table 3 Example 5-2

[0079]

[Chemical 38]

N, N'-ditosyl-1,3-propanediamine (15a) and compound 1 were prepared in the same manner as in Example 5-1.
In the reaction of 6, N ⁴ , N ⁸ -ditosyl-4,8-diaza-
1,11-Undecanediol (17a) was obtained as a viscous liquid with a yield of 90%. Compound _{17a: C 23 H 34 O 6} N 2 S 2 (498.650) Analysis Calculated: C, 55.40; H, 6.87 ; N, 5.62; S,
12.86% Actual value: C, 55.36; H, 6.87; N, 5.52; S, 12.70% IR (KRS) ν 3530 (OH), 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Examples 5-3

[0081]

[Chemical Formula 39]

In the same manner as in Example 5-1, by reacting N, N'-ditosyl-1,2-ethanediamine (11a) with 2-bromoethanol (12), N, N'-bis (2-
Hydroxyethyl-N, N'-ditosyl-1,2-ethanediamine (13a) was recrystallized from methanol and obtained in a yield of 85%. Compound 13a: C ₂₀ H ₂₈ O ₆ N ₂ S ₂ (456.572) mp 150 to 152 ° C. (recrystallized from methanol) Calculated by elemental analysis: C, 52.61; H, 6.18; N, 6.14; S,
14.05% Actual value: C, 52.93; H, 6.20; N, 6.21; S, 13.93% IR (KBr) ν 3350 (OH), 1325, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Examples 5-4

[0083]

[Chemical 40]

In the same manner as in Example 5-1, N ¹ , N ³ , N ⁵
- Toritoshiru -3-reaction of aza-1,7-heptane diamine and (11b) with compound ^{12, N 3, N 6,} N 9 - Toritoshiru 3,6,9-triaza-1,11-undecane diol ( 13b) was obtained as a viscous liquid with a yield of 99%. Compound 13b: C ₂₉ H ₃₉ O ₈ N ₃ S ₃ (653.824) calculated by elemental analysis: C, 53.27; H, 6.01; N, 6.43; S,
14.71% Found: C, 52.84; H, 6.02; N, 6.40; S, 14.57% IR (KRS) ν 3530 (OH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Examples 5-5

[0085]

[Chemical 41]

In the same manner as in Example 5-1, N ¹ , N ³ , N ⁶ ,
The reaction of N ⁸ -tetratosyl-3,6-diaza-1,8-octanediamine (11c) with compound 12 produces N ³ , N
^6, N ^9, N ¹² - Tetoratoshiru-3,6,9,12-tetraaza-1,14-tetradecane diol (13c) is recrystallized from methanol, it was obtained in 70% yield. Compound 13c: C ₃₈ H ₅₀ O ₁₀ N ₄ S ₄ (851.076) mp 195 to 197 ° C. Elemental analysis calculated value: C, 53.62; H, 5.92; N, 6.58; S, 1
5.07% Found: C, 53.35; H, 5.87; N, 6.58; S, 14.92% IR (KRS) ν 3410 (OH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Diol → Dimesyl ester Example 6-1

[0087]

[Chemical 42]

O ¹ , O ¹² -dimedyl-N ⁴ , N ⁹ -ditosyl-4,9-diaza-1,12-dodecanediol (18
b): Compound 17b (1.50 g) obtained in Example 5-1 was mixed in methylene chloride (40 ml) to give methanesulfonyl chloride.
(0.57 ml, 2.5 molar equivalents with respect to 17b) and triethylamine (1.42 ml, with respect to methanesulphonyl chloride, 2.5
(Double volume) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure and subjected to silica gel column chromatography (eluent: chloroform: acetone 9: 1 v / v (300 ml) → 4: 1 (200 ml).
→ 7: 3 (100 ml)), to obtain 1.47 g (yield 75%) of Compound 18b as an amorphous powder. Compound _{18b: C 26 H 40 O 10} N 2 S 4 (668.86) Analysis Calculated: C, 46.69; H, 6.03 ; N, 4.19; S,
19.18% Measured value: C, 46.33; H, 5.95; N, 4.17; S, 19.15% IR (KBr) ν 1340, 1325, 1170, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Example 6 -2

[0089]

[Chemical 43]

By reacting the compound 17a obtained in Example 5-2 with methanesulfonyl chloride in the same manner as in Example 6-1, O ¹ , O ¹¹ -dimezyl-N ⁴ , N ⁸ -ditosyl-4,8 was prepared.
-Diaza-1,11-undecanediol (18a) was obtained as a viscous liquid with a yield of 85%. Compound 18a: C ₂₅ H ₃₈ O ₁₀ N ₂ S ₄ (654.834) Calculated by elemental analysis: C, 45.85; H, 5.85; N, 4.28; S,
19.59% Found: C, 45.50; H, 5.74; N, 4.02; S, 19.50% IR (KRS) ν 1340, 1320, 1170, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Example 6 -3

[0091]

[Chemical 44]

By reacting compound 13a obtained in Example 5-3 with methanesulfonyl chloride in the same manner as in Example 6-1, N, N'-bis (2-medyloxyethyl) -N,
N'-ditosyl-1,2-ethanediamine (14a) was recrystallized from methanol and obtained in a yield of 84%. Compound 14a: C ₂₂ H ₃₂ O ₁₀ N ₂ S ₄ (612.756) mp 144 to 145 ° C. Elemental analysis calculated value: C, 43.12; H, 5.26; N, 4.57; S,
20.93% Measured value: C, 43.28; H, 5.22; N, 4.47; S, 20.83% IR (KBr) ν 1340, 1330, 1180, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Example 6 -4

[0093]

[Chemical formula 45]

The reaction of the compound 13b obtained in Example 5-4 with methanesulfonyl chloride in the same manner as in Example 6-1 gave O ¹ , O ¹¹ -dimezyl-N ³ , N ⁶ , N ⁹ -tritosyl-.
3,6,9-Triaza-1,11-undecanediol (14b) was obtained as a viscous liquid with a yield of 99%. Compound 14b: C ₃₁ H ₄₃ O ₁₂ N ₃ S ₅ (810.008) Calculated by elemental analysis: C, 45.96; H, 5.35; N, 5.19; S, 1
9.79% Found: C, 45.78; H, 5.26; N, 4.96; S, 19.76% IR (KBr) v 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3 Example 6-5

[0095]

[Chemical formula 46]

By the reaction of the compound 13c obtained in Example 5-5 with methanesulfonyl chloride in the same manner as in Example 6-1, O ¹ , O ¹⁴ -dimedyl-N ³ , N ⁶ , N ⁹ , N ^{12 was obtained.} -Tetratosyl-3,6,9,12-tetraaza-1,14-tetradecanediol (14c) was obtained as a viscous liquid in a yield of 99%.
Obtained in. Compound 14c: C ₄₀ H ₅₄ O ₁₄ N ₄ S ₆ (1007.26) calculated by elemental analysis: C, 47.69; H, 5.40; N, 5.56; S,
19.01% Measured value: C, 47.41; H, 5.34; N, 5.38; S, 18.94% IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 3

[0097]

[Table 3]

Example 7

[0099]

[Chemical 47]

N, N-bis (3-bromopropyl) benzylamine (19): benzylamine (1.563 g), 1,3-dibromopropane (1 in acetonitrile (80 ml).
A mixture of 4.726 g, 5 molar equivalents based on benzylamine) and sodium hydrogen carbonate (3.67 g, 3 equivalents based on benzylamine) was stirred at about 60 ° C. for 22 hours. The reaction solution was filtered through Celite, the filtrate was concentrated, and silica gel column chromatography [eluent chloroform: acetone 95: 5 v / v (300
ml) → 9: 1 (200 ml)], Compound 19 (Rf = 0.7 (developing solution chloroform: acetone 95: 5)) was obtained as a colorless liquid in a yield of 37%. Compound 19: C ₁₃ H ₁₉ NBr ₂ (349.1) SIMS (NBA) m / z 348,350 (M + H) ⁺ NMR (CDCl ₃ ): δ 2.60 (4H, 6-S, BnN- CH ₂ ) 2.02 (4H, 6 _{-S, BnN-CH 2 - CH} 2) 3.45 (4H, t, J = 6.50, CH 2 -Br) N- synthesis example of monobenzyl cyclic polyamine 8-1

[0101]

[Chemical 48]

N ¹ -benzyl-N ⁵ , N ⁹ -ditosyl-
1,5,9-Triazacyclododecane (20): DMF
(160ml) in the compound 3b (5.834g) obtained in Example 1-1,
A mixture of 1,3-dibromopropane (2.7 g, 1.2 molar equivalents based on 3b) and potassium carbonate (22.83 g, 15 molar equivalents based on 3b) was stirred at room temperature for 4 days. The reaction solution was filtered through Celite and concentrated. The residue was purified by silica gel column chromatography (eluent chloroform: acetone 97: 3v /
v (600 ml)) and the fractions containing Compound 20 were collected and concentrated. It was dissolved in a small amount of chloroform, recrystallized by adding methanol, and 3.20 g of compound 20 (yield 52%, conversion rate
82%) was obtained. Compound 20: C ₃₀ H ₃₉ O ₄ N ₃ S ₂ (569.768) mp 201 to 203 ° C. SIMS 570 m / z (M + H) ⁺ elemental analysis calculated value: C, 63.24; H, 6.90; N, 7.38; S,
11.26% Found: C, 63.04; H, 6.88; N, 7.10; S, 11.15% IR (KBr) v 1330, 1160 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 8-2

[0103]

[Chemical 49]

By reacting compound 3a obtained in Example 1-2 with dibromopropane in the same manner as in Example 8-1, N ^1-
Benzyl -N ^4, N ⁸ - ditosylate 1,4,8-triazacyclododecane (21) was obtained in 39% yield as an amorphous powder. Compound 21: C ₂₈ H ₃₅ O ₄ N ₃ S ₂ (541.716) Calculated by elemental analysis: C, 62.08; H, 6.51; N, 7.76; S,
11.84% Found: C, 62.24; H, 6.39; N, 7.50; S, 11.82% IR (KRS) v 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 8-3

[0105]

[Chemical 50]

By reacting the compound 7c obtained in Example 4-1 with 1,3-dibromopropane in the same manner as in Example 8-1, N ¹ -benzyl-N ⁵ , N ⁹ , N ¹³ , N ^{17 was used.} -Tetratosyl-1,5,9,13,17-pentaazacycloeicosane (22) was obtained as an amorphous powder in a yield of 78%. Compound 22: C ₅₀ H ₆₇ O ₈ N ₅ S ₄ (994.340) Calculated by elemental analysis: C, 60.39; H, 6.79; N, 7.04; S,
12.90% Actual value: C, 60.40; H, 6.56; N, 6.80; S, 12.67% IR (KRS) ν 1330, 1160 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 8-4

[0107]

[Chemical 51]

By reacting the compound 10b obtained in Example 4-3 with 1,3-dibromopropane in the same manner as in Example 8-1, N ¹ -benzyl-N ⁴ , N ⁸ , N ¹² , N ^{16 was used.} , N ²⁰ , N ²⁴
-Hexatosyl-1,4,8,12,16,20,24
-Heptaazacyclohexacosane (23) was obtained as amorphous powder with a yield of 58%. Compound 23: C ₆₈ H ₈₇ O ₁₂ N ₇ S ₆ (1386.828) calculated by elemental analysis: C, 58.89; H, 6.32; N, 7.07; S,
13.87% Measured value: C, 58.78; H, 6.20; N, 6.74; S, 13.77% IR (KBr) v 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 9-1

[0109]

[Chemical 52]

N ¹ -benzyl-N ⁵ , N ¹⁰ , N ¹⁴ , N ¹⁸ ,
N ^22, N ²⁷ - Hekisatoshiru -1,5,10,14,1
8,22,27-heptaazacyclotricontane (26
b): Compound 7 obtained in Example 4-2 in DMF (90 ml)
d (1.12 g), compound 18a obtained in Example 6-2 (0.845 g,
1.13 molar equivalents relative to 7d) and potassium carbonate (1.57
g, 10 molar equivalents relative to 7d) was stirred at room temperature for 4 days. The reaction solution was filtered through Celite, the filtrate was concentrated, and the residue was subjected to silica gel column chromatography [eluent: chloroform: acetone 93: 7 v / v (800 ml)]. The fractions were collected and concentrated to give compound 26b as an amorphous powder. , With a yield of 41%. Compound _{26b: C 72 H 95 O 12} N 7 S 6 (1442.932) Analysis Calculated: C, 59.93; H, 6.64 ; N, 6.80; S,
13.33% Found: C, 59.67; H, 6.66; N, 6.49; S, 13.33% SIMS (NBA) m / z 1442 (M + H) ⁺ IR (KBr) ν 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl) ₃ ) Table 4 Example 9-2

[0111]

[Chemical 53]

By reacting the compound 7c obtained in Example 4-1 with the compound 18b obtained in Example 6-1 in the same manner as in Example 9-1, N ¹ -benzyl-N ⁵ , N ⁹ , N ^{13 was obtained.} , N ¹⁸ , N ²² , N ²⁶
-Hexatosyl-1,5,9,13,18,22,26
-Heptaazacyclononacosane (26a) was obtained as an amorphous powder in a yield of 52%. Compound 26a: C ₇₁ H ₉₃ O ₁₂ N ₇ S ₆ (1428.906) Calculated by elemental analysis: C, 59.68; H, 6.56; N, 6.86; S,
13.47% Found: C, 59.88; H, 6.56; N, 6.79; S, 13.15% SIMS (NBA) m / z 1428 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl) ₃ ) Table 4 Example 9-3

[0113]

[Chemical 54]

By reacting the compound 3a obtained in Example 1-2 with the compound 14a obtained in Example 6-3 in the same manner as in Example 9-1, N ¹ -benzyl-N ⁴ , N ⁷ , N was obtained. ¹⁰ , N ¹³ -Tetratosyl-1,4,7,10,13-pentaazacyclopentadecane (24a) was obtained as an amorphous powder in a yield of 36%. Compound 24a: C ₄₅ H ₅₅ O ₈ N ₅ S ₄ (922.194) calculated by elemental analysis: C, 58.61; H, 6.01; N, 7.60; S,
13.91% Found: C, 58.56; H, 5.94; N, 7.35; S, 14.10% SIMS (NBA) m / z 922 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR ( CDCl ₃₎ table 4 example 9-4

[0115]

[Chemical 55]

In the same manner as in Example 9-1, the reaction of the compound 3a obtained in Example 1-2 with the compound 14b obtained in Example 6-4 was carried out to produce N ¹ -benzyl-N ⁴ , N ⁷ , N. ¹⁰ , N ¹³ , N ¹⁶ −
Pentatosyl-1,4,7,10,13,16-hexaazacyclooctadecane (24b) was obtained as an amorphous powder in a yield of 41%. Compound 24b: C ₅₄ H ₆₆ O ₁₀ N ₆ S ₅ (1119.446) calculated by elemental analysis: C, 57.93; H, 5.94; N, 7.51; S,
14.32% Found: C, 57.74; H, 5.80; N, 7.37; S, 14.21% SIMS (NBA) m / z 1120 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR ( CDCl ₃₎ table 4 example 9-5

[0117]

[Chemical 56]

Compound 3a obtained in Example 1-2 and compound 14c obtained in Example 6-5 in the same manner as in Example 9-1.
Reaction with N ¹ -benzyl-N ⁴ , N ⁷ , N ¹⁰ , N ¹³ ,
N ^16, N ¹⁹ - Hekisatoshiru -1,4,7,10,13,
16,19-Heptaazacycloheneicosane (24c)
Was obtained as an amorphous powder with a yield of 37%. Compound _{24c: C 63 H 77 O 12} N 7 S 6 (1316.698) Analysis Calculated: C, 57.46; H, 5.90 ; N, 7.45; S,
14.61% Found: C, 57.35; H, 5.87; N, 7.35; S, 14.56% SIMS (NBA) m / z 1316 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR ( CDCl ₃₎ table 4 example 9-6

[0119]

[Chemical 57]

Compound 3b obtained in Example 1-1 and compound 18b obtained in Example 6-1 in the same manner as in Example 9-1.
The reaction with N ¹ -benzyl-N ⁵ , N ⁹ , N ¹⁴ , N ¹⁸ -tetratosyl-1,5,9,14,18-pentaazacyclohenecosane (25) as an amorphous powder yielded 58%. (Conversion rate 100%). Compound 25: C ₅₁ H ₆₇ O ₈ N ₅ S ₄ (1006.35) calculated by elemental analysis: C, 60.87; H, 6.71; N, 6.96; S,
12.75% Found: C, 60.47; H, 6.67; N, 6.93; S, 12.59% SIMS (NBA) m / z 1006 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR ( CDCl ₃₎ table 4 N, N'synthesis example of dibenzyl cyclic polyamine 10-1

[0121]

[Chemical 58]

N ¹ , N ¹³ -dibenzyl-N ⁵ , N ⁹ , N ¹⁷ , N
²¹ -Tetratosyl-1,5,9,13,17,21-hexaazacyclotetracosane (27b): DMF (70 m
l), the compound 7c (0.70 g) obtained in Example 4-1, the compound 19 obtained in Example 7 (1.183 molar equivalent with respect to 0.283 g, 10 c) and potassium carbonate (1.02 g, with respect to 10 c). The mixture (10 molar equivalents) was stirred at room temperature for 4 days. The reaction solution was filtered through Celide, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography [eluent: chloroform: acetone 93: 7 v / v (500 ml)] to obtain Compound 27b as an amorphous powder in a yield of 54% (conversion rate 67%). Compound 27b: C ₆₀ H ₇₈ O ₈ N ₆ S ₄ (1139.536) calculated by elemental analysis: C, 63.24; H, 6.90; N, 7.38; S,
11.26% Found: C, 63.27; H, 6.72; N, 7.05; S, 11.25% SIMS (NBA) m / z 1140 (M + H) ⁺ IR (KBr) ν 1330, 1150 (SO ₂ ) cm ^-1 NMR ( CDCl ₃₎ table 4 example 10-2

[0123]

[Chemical 59]

Example 1-1 Similar to Example 10-1
The reaction of the compound 3b obtained in Example ¹ with the compound 19 obtained in Example 7 gave N ¹ , N ⁹ -dibenzyl-N ⁵ , N ¹³ -ditosyl-1,
5,9,13-Tetraazacyclohexadecane (27
a) was obtained and recrystallized from chloroform-methanol to give a yield of 40%. Compound 27a: C ₄₀ H ₅₂ O ₄ N ₄ S ₂ (716.98) mp 123 to 124 ° C. Elemental analysis calculated value: C, 67.00; H, 7.31; N, 7.82; S,
8.95% Found: C, 67.16; H, 7.34; N, 7.93; S, 8.93% IR (KBr) ν 1150, 1330 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 10-3

[0125]

[Chemical 60]

Example 4-2 as in Example 10-1
The reaction of the compound 7d obtained in Example 7 with the compound 19 obtained in Example 7 yielded N ¹ , N ¹⁴ -dibenzyl-N ⁵ , N ¹⁰ , N ¹⁸ , N ²³ -tetratosyl-1,5,10,14,18, 23-Hexaazacyclohexacosane (27c) was obtained and recrystallized from chloroform-methanol to give 59% yield. Compound 27c: C ₆₂ H ₈₂ O ₈ N ₆ S ₄ (1167.588) mp 184 to 186 ° C. Elemental analysis calculated value: C, 63.77; H, 7.08; N, 7.20; S,
10.99% Found: C, 63.55; H, 7.04; N, 7.04; S, 11.12% IR (KBr) v 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 Example 10-4

[0127]

[Chemical formula 61]

Example 4-5 in the same manner as Example 10-1
The reaction of the compound 10d obtained in 1) with the compound 19 obtained in Example 7 gave N ¹ , N ¹⁸ -dibenzyl-N ⁵ , N ⁹ , N ¹⁴ , N ²² ,
N ²⁷ , N ³¹ -hexatosyl-1,5,9,14,18,
22,27,31-Octazacyclotetratriacontane (28) was obtained as an amorphous powder at a rate of 43%. Compound 28: C ₈₂ H ₁₀₈ O ₁₂ N ₈ S ₆ (1590.144) calculated by elemental analysis: C, 61.93; H, 6.85; N, 7.05; S,
12.10% Found: C, 61.89; H, 6.73; N, 6.88; S, 12.21% IR (KBr) v 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 4 FABMS (NBA) m / z 1589 (M + H) ⁺

[0129]

[Table 4]

Derivatization of Cyclic Amines with De-N-benzyl Example 11-1

[0131]

[Chemical formula 62]

N ⁵ , N ¹⁰ , N ¹⁴ , N ¹⁸ , N ²² , N ²⁷ -hexatosyl-1,5,10,14,18,22,27-heptaazacyclotriacontane (34b): acetic acid (28 m
l) in compound 26b (0.534 g) obtained in Example 9-1.
And 10% palladium-carbon were mixed, and reduction was performed with hydrogen at an average pressure of 4.6 kg / cm ² for a total of 66 hours. The reaction solution was filtered through Celite, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography [eluent: chloroform: methanol 95: 5 v / v (400 ml)] to obtain 0.376 g (yield 75%) of Compound 34b as an amorphous powder. Compound 34b: C ₆₅ H ₈₉ O ₁₂ N ₇ S ₆ (1352.814) calculated by elemental analysis: C, 57.71; H, 6.63; N, 7.25; S,
14.22% Found: C, 57.81; H, 6.49; N, 6.94; S, 14.22% SIMS (NBA) m / z 1352 (M + H) ⁺ IR (KBr) ν 2300-2700 (NH ⁺ ), 1330, 1150 (SO ₂ )
cm ^-1 NMR (CDCl ₃ ) Table 5 Example 11-2

[0133]

[Chemical formula 63]

Example 9-same as Example 11-1
Hydrogenation of the compound 26a obtained in Step 2 gave N ⁵ , N ⁹ , N ¹³ , N
¹⁸ , N ²² , N ²⁶ -hexatosyl-1,5,9,13,1
8,22,26-heptaazacyclotriacontane (3
4a) was obtained as an amorphous powder with a yield of 75%. Compound 34a: C ₆₄ H ₈₇ O ₁₂ N ₇ S ₆ (1338.788) SIMS (NBA) m / z 1340 (M + H) ⁺ IR (KBr) ν 3400 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃₎ table 5 example 11-3

[0135]

[Chemical 64]

Example 8-same as Example 11-1.
When compound 20 was obtained in 1 is hydrogenated, N ^5, N ⁹ - ditosylate 1,5,9 triazacyclododecane (29) was obtained as a thick liquid in 99% yield. Compound _{29: C 23 H 33 O 4} N 3 S 2 (479.65) Analysis Calculated: C, 57.59; H, 6.94 ; N, 8.76; S,
13.37% Found: C, 57.64; H, 6.75; N, 8.58; S, 13.42% SIMS (NBA) m / z 481 (M + H) ⁺ IR (KBr) ν 3350 (NH), 1330, 1160 (SO). ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5 Example 11-4

[0137]

[Chemical 65]

In the same manner as in Example 11-1, Example 8-
When the compound 23 obtained in 4 was hydrogenated, N ⁴ , N ⁸ , N ¹² ,
^{N 16, N 20, N 24} - Hekisatoshiru -1,4,8,12,
16,20,24-Heptaazacyclohexacosane (3
1) was obtained as an amorphous powder with a yield of 83%. IR (KRS) ν 3400 (NH ), 1340, 1160 (SO 2) cm -1 NMR (CDCl 3) Table 5 Example 11-5

[0139]

[Chemical formula 66]

Example 9-same as Example 11-1
When the compound 25 obtained in 6 was hydrogenated, N ⁵ , N ⁹ , N ¹⁴ ,
N ¹⁸ -tetratosyl-1,5,9,14,18-pentaazacycloheneicosane (33) was used as an amorphous powder,
The yield was 86%. Compound 33: C ₄₄ H ₆₁ O ₈ N ₅ S ₄ (916.232) Calculated by elemental analysis: C, 57.68; H, 6.71; N, 7.64; S,
14.00% Actual value: C, 57.71; H, 6.54; N, 7.52; S, 14.08% IR (KRr) ν 3370 (NH), 1330, 1150 (SO ₂ ) cm ^-1 SIMS (NBA) m / z 916 ( M + H) ⁺ NMR (CDCl ₃ ) Table 5 Examples 11-6

[0141]

[Chemical formula 67]

Example 10 was conducted in the same manner as in Example 11-1.
When the compound 27b obtained in step 1 was hydrogenated, N ⁵ , N ⁹ , N ¹⁷ ,
N ²¹ - Tetoratoshiru -1,5,9,13,17,21-
Hexaazacyclotetracosane (35b) was obtained as an amorphous powder with a yield of 86%. Compound _{35b: C 46 H 66 O 8} N 6 S 4 (959.3) Analysis Calculated: C, 57.90; H, 6.94 ; N, 8.76; S,
13.37% Actual value: C, 57.59; H, 6.83; N, 8.95; S, 13.41% IR (KBr) v 3400 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5 Examples 11-7

[0143]

[Chemical 68]

Example 9-same as Example 11-1
When the compound 24a obtained in 3 was hydrogenated, N ⁴ , N ⁷ ,
N ^10, N ¹³ - Tetoratoshiru -1,4,7,10,13 penta azacyclopentadecan (32a) was obtained in 89% yield as an amorphous powder. Compound _{32a: C 38 H 59 O 8} N 5 S 4 (842.156) Analysis Calculated: C, 54.19; H, 7.06 ; N, 8.32; S,
15.23% Measured value: C, 54.04; H, 6.91; N, 8.06; S, 15.08% IR (KBr) ν 3400 (NH), 1320, 1145 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5 Examples 11-8

[0145]

[Chemical 69]

Example 9-same as Example 11-1.
When the compound 24b obtained in 4 was hydrogenated, N ⁴ , N ⁷ ,
N ¹⁰ , N ¹³ , N ¹⁶ -pentatosyl-1,4,7,10,
13,16-Hexaazacyclooctadecane (32b)
Was obtained as an amorphous powder with a yield of 71%. Compound _{32b: C 47 H 60 O 10} N 6 S 5 (1029.328) Analysis Calculated: C, 54.84; H, 5.88 ; N, 8.17; S,
15.58% Measured value: C, 54.64; H, 5.98; N, 8.06; S, 15.44% IR (KBr) ν 3240 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5 Examples 11-9

[0147]

[Chemical 70]

Example 9-same as Example 11-1
When the compound 24c obtained in Step 5 was hydrogenated, N ⁴ , N ⁷ ,
^{N 10, N 13, N 16} , N 19 - Hekisatoshiru 1,4,7,
10,13,16,19-heptaazacycloheneicosane (32c) was obtained as an amorphous powder with a yield of 50%. Compound 32c: C ₅₆ H ₇₁ O ₁₂ N ₇ S ₆ (1226.58) Calculated by elemental analysis: C, 54.83; H, 5.84; N, 7.99; S,
15.69% Found: C, 54.63; H, 5.75; N, 7.81; S, 15.40% IR (KBr) v 3400 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5 Examples 11-10

[0149]

[Chemical 71]

Example 10 was carried out in the same manner as Example 11-1.
When the compound 27a obtained -2 hydrogenation, N ^5, N ¹³ -
Ditosyl-1,5,9,13-tetraazacyclohexadecane (35a) was obtained as an amorphous powder with a yield of 90%. Compound _{35a: C 26 H 40 O 4} N 4 S 2 (536.744) Analysis Calculated: C, 58.18; H, 7.51 ; N, 10.44; S,
11.95% Found: C, 57.93; H, 7.43; N, 10.15; S, 11.80% IR (KBr) ν 3400 (NH), 1330, 1150 (SO ₂ ) cm ^-1 Examples 11-11

[0151]

[Chemical 72]

Example 10 was carried out in the same manner as Example 11-1.
When the compound 27c obtained in -3 was hydrogenated, N ⁵ , N ¹⁰ ,
N ^18, N ²³ - Tetoratoshiru -1,5,10,14,1
8,23-Hexaazacyclohexacosane (35c) was obtained as an amorphous powder with a yield of 95%. Compound _{35c: C 48 H 70 O 8} N 6 S 4 (987.352) Analysis Calculated: C, 58.39; H, 7.15 ; N, 8.51; S,
12.99% Actual value: C, 58.11; H, 7.10; N, 8.38; S, 12.78% IR (KBr) ν 3400 (NH), 1330, 1150 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ) Table 5

[0153]

[Table 5]

Cyclic amine N- (ω-bromoalkyl
Reduction) Example 12-1

[0155]

[Chemical formula 73]

N ^1- (3-bromopropyl) -N ⁵ , N ⁹
-Ditosyl-1,5,9-triazacyclododecane (3
6): Compound 29 (0.411 g) obtained in Example 11-3, 1,3-dibromopropane (1.
73 g, 10 molar equivalents to 29), sodium hydrogen carbonate
(0.36g, 5 molar equivalents to 29) Mix the mixture at about 60 ° C for 15
Stir for hours. The reaction solution was filtered through Celite, concentrated, and subjected to silica gel column chromatography [eluent, chloroform: methanol 95: 5 v / v (300 ml)] to obtain 0.23 g of Compound 36 as an amorphous powder (yield 43 %) Obtained. Compound 36: C ₂₆ H ₃₈ O ₄ N ₃ S ₂ Br (600.636) SIMS (NBA) m / z 601,602 (M + H) ⁺ IR (KBr) ν 1330, 1155 (SO ₂ ) cm ^-1 NMR (CDCl ₃ ): Δ1.76 (4H, quin, NCH ₂ - CH ₂ -CH ₂ N) 1.87 (2H, quin, NCH ₂ - CH ₂ -CH ₂ N) 1.95 (2H, b-quin, NCH ₂ - CH _2- CH ₂ Br) 2.43 (ArMe) 2.48 (4H, bt, NCH ₂ -CH ₂ - CH ₂ N) 2.52 (2H, bt, N CH ₂ -CH ₂ -CH ₂ Br) 3.14 (4H, t, J = 6.4 , N CH ₂ -CH ₂ -CH ₂ N) 3.20 (4H, t, J = 6.71, NCH ₂ -CH ₂ - CH ₂ N) 3.42 (2H, t, J = 6.4, NCH ₂ -CH ₂ - CH ₂ Br) 7.31 (ArHme) 7.65 (ArHs) Example 12-2

[0157]

[Chemical 74]

Example 11 was carried out in the same manner as Example 12-1.
By reacting the compound 34b obtained in -1 with 1,3-dibromopropane, N ^1- (3-bromopropyl) -N ⁵ , N ¹⁰ , N
¹⁴ , N ¹⁸ , N ²² , N ²⁷ -hexatosyl-1,5,10,
14,18,22,27-heptaazacyclotriacontane (37) was obtained as an amorphous powder in a yield of 21%. Compound 37: C ₆₈ H ₉₄ O ₁₂ N ₇ S ₆ Br (1473.8) SIMS (NBA) m / z 1474 (M + H) ⁺

Claims (3)

[Claims] 1. A compound represented by the following general formula (I): [Chemical 1] (In the formula, R ¹ is a hydrogen atom or a group represented by the formula 2, R ² is a hydrogen atom or a group represented by the formula 3, and R ³ is CHO. Group or a Ts group, or R ² and R ³ are Phth groups, and R ^{2 in} the formula
⁴ represents a hydrogen atom, R ⁵ represents a CHO group or a Ts group, or R ⁴ and R ⁵ represent a Phth group, and n, m and p are each independently an integer of 2 to 4. ) [Chemical 2] [Chemical 3] 2. A compound represented by the following general formula (II) or (III). [Chemical 4] [Chemical 5] (In the formula of Chemical formula 4, R ⁶ represents a group represented by the formula of Chemical formula 6 or Chemical formula 7 below (wherein n is an integer of 0 to 2; Is 3 or 4.), R ⁷ represents a hydrogen atom, an Ms group or a Ts group, and m is 2 or 3. In the formula of Chemical formula 5, q is an integer of 2 to 4.) 6] [Chemical 7] 3. A compound represented by the following general formula (IV). [Chemical 8] (In the formula of Chemical formula 8, R ⁸ represents a hydrogen atom, a Bn group, or a group represented by the chemical formula of Chemical formula 9 (wherein, r is an integer of 2 to 4), and R ⁹ is Represents a hydrogen atom or a Bn group, and m is 1
Or 2, n1, n2, p1 and p2 are each independently an integer of 1 to 3, x1 and x2 are each independently 1 or 2, and y1 and y2 are each independently 0,
1 or 2, and z is 0 or 1. ) [Chemical 9]