JPS6383077A - Novel cyclic polyaza compound and its manufacturing method - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a novel cyclic polyaza compound, and more particularly to a novel polyaza Cm] (2,5) pyridinophane and polyaza (ml valacyclophane) and a method for producing the same. [Background of the Invention] The present invention They previously synthesized dithia(2,5)pyridinophane and diaza(2,5)pyridinophane, which have chemical structures and properties similar to coenzyme B6, and investigated their properties (1 (a) Iwata et al. , Chemistry Letters (1976), 983; (5) Kuzuhara et al., Journal of the American Chemical Society 9
9 4173 (1977); (C) Kuzuhara et al., Tetrahedron Letters, (1978). 3563; (d) Iwata et al., Chemistry Letters, (1981), 5; (e) Kuzuhara et al., Chemistry Letters, (1982), 1765.1769; (r) Kuzuhara et al., Bulletin of the Chemical Society
of Japan, 55.829 (1982). 56.2263.3652 (1983); 57°23
7 (1984); (1110 Iwata et al., Bulletin of the Chemical
Society of Japan, 58, 2502 (198
5): 2(a) Iwata et al., Chemistry Recourse, (1981), 1749; et al.) Iwata et al., Journal
of organic chemistry〕[:1)a) M
, Iwata, Ho ni uzuhara, and S
, Emoto. Chem, Lett,, 1 9 7 6, 9
8 3 ; b) H, Kuzuhara. M., Iwata, and S., Emoto, J.
, Am, Chem, Soc. 99, 4173 (1977) ;c) HlKuzu
hara. T, Komatsu, and S, Emoto,
Tetrahedron Lett. 1978, 3563; M, Iwata and
H. Kuzuhara. Chem, Lett,, l 981, 5; e
) y, Tachibana. M., Ando, and H. Kuzuhara, C.
hem, Lemt,, 1982゜1765 and
1769; f)! J, Ando. Y, Tachibana, and H, Kuzuha
ra, Bull, Chem. Sac, Jpn, 55.829 (1982), 56
．． 2263 and 3652 (1983); 57, 2
37 (1984); g)! J, Iwata a
nd H, Kuzuhara. Bull, Chem, Soc, Jpn, 58.
2502 (1985):2)a)~! ,Iwat
a and H9Kuzuhara, Chem,
Lett. 1981, 1749: b) M, Iwata a.
nd Ho Kuzuhara. J,Org,Chem,,48. 1282 (198
3) ). These synthetic coenzymes have excellent stereoselectivity toward specific amino acids, are significantly more stable, and exhibit superior effects compared to natural coenzymes. The inventors further designed a novel synthetic coenzyme with an additional site for host-guest complex formation by containing a functional group on the bridging group C3.
(a) Kubushi et al., Journal of the American
Chemical Society, Plate 6486 (1981); (5
) Mokudo et al., Ibid., 105°2063 (1983); (
C) Tsukube, Journal of the Chemical Society, Chemical Communication, (1983),
970 3(a)1, Tabushi, Y, Kimu
ra, and jamakura, J. Am. Chem, Soc, 103.6486 (1981)
;b) 11i, Kimura, A, Watanabe
, and M, Kodama, 1bid,. 105, 2063 (1983) ;c) H, Tsu
Kube. J, Chem, Soc, Chem, Commun
,, 1983.970)]. Metabolic reactions of amino acids in living organisms are carried out by holoenzyme consisting of coenzyme vitamin B6 and apoenzyme. In this case, vitamin B6 is actually involved in the chemical conversion (catalytic action), and the role of the enzyme is thought to be to take in the substrate and understand and control its stereochemistry. A molecule that retains the catalytic properties of vitamin B6 and is capable of capturing a substrate molecule and recognizing its stereochemistry has not yet been synthesized, and there is widespread interest in whether it is possible to create such a highly functional molecule. are collecting. As described above, the present inventors succeeded in realizing part of the intended function by modifying the vitamin 86 molecule and imparting constrained rotation. Based on these results, the present inventors designed and synthesized a molecule that maintains constrained rotation, has the function of incorporating guest molecules, and also has a catalytic function, verified each function, and developed the present invention. The invention was completed. [Object of the Invention] An object of the present invention is to provide a simpler functional molecule that has both the functions of an enzyme and the functions of vitamin B6. Another object of the present invention is to provide a method for synthesizing a compound potentially having such functions in high yield. [Structure of the Invention] The novel cyclic polyaza compound of the present invention is represented by the following general formula. [In the formula, TS badruenesulfonyl group, n represents 1 to 3 (R represents a hydrogen atom or a lower alkyl group). ] Specific examples of the compounds included in the above general formula include those shown below. 8a I CH3 9a 2 CH3 10a 3 CH38b
IH 9b 2
110b, '3
H compound n 11. 1 The above compound is a compound represented by the general formula (I): (wherein Ts is a toluenesulfonyl group and n is an integer of 1 to 3) and a general formula () is a nylkyl group. ) is shown. ] can be synthesized by reacting the compound represented by the following in the presence of a dehalogenating and hydrogenating agent. Specific examples of compounds represented by general formula (I) include compounds 1 (Tl=1), 2 (n=2)
, 3 (n=3). Moreover, general formula (II)
As specific examples of compounds represented by, the reaction between the compound of general formula (I) and the compound of general formula (n) is dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylenephosphorotriamine (HMPA). In polar solvents such as K2CO3, Na2C
O = , K) lcOa, 2 to 2
4 hours is sufficient. Compounds (1), (2), (
3) is N-(2-bromoethyl)tosylamide (6)
and N,N'-cytosyl-1,2-ethanediamine (7
) can be obtained by reaction with Compound (4a) was prepared using the method of Iwata et al.
of the chemical society of japan 55
．． 2295 (1982)], and compound (4b) can be synthesized by the method of Iwata et al. [Iwata et al., Journal of Organic Chemistry, 48° 1282 (1983)]. [Example] JEOLJNM-GX40 in CD CL as an internal a-half of Luha, Me, and Si
0 (400MHz) recorded on a spectrometer;
Chemical shifts (δ) and coupling constants (J) are in parts per million (ppm) and Hertz, respectively. Infrared spectra were measured with a Takao IR-27G spectrometer as a KBr disk. Mass spectrum (MS, relative intensity) was performed using Hitachi RMLI6.
Obtained on a Me spectrometer, direct in left method, ionization potential of 208 V, and sample and chamber temperature of 230°C. For column chromatography, Merck silica gel 60 (ART, 7734.0.
063-0.20) was used. Merck prechotide silica gel 60 for thin layer chromatography (TLC)
F254 plate (art, 5715, 20X20c
m) was used. Column chromatography and TLC
for. Two solvent systems were used unless otherwise stated. That is, benzene-acetone 9:1 v/v (solvent Δ), tochloroform acetone 93:7 v/v (solvent B
). Product spots on TLC were detected using a U■ lamp or in an iodine vapor bath. N
, N-dimethylformamide (DMF) was dried over molecular sieves (type A). The supernatant was then used directly for the reaction. Uncorrected melting points were measured with a micro melting point apparatus (Yanagimoto Seisakusho, Serial N. 2647). N, N'
- Cytosyl-1,2-ethanediamine (7) was prepared using a previously reported method [Iwata et al., Bulletin of Chemical Society of Japan. 2153 (1982)) from 1,2-ethanediamine. 5'-deoxy-2', 5'
-dichloro-3,4'-0-inpropylidene-6-methylpyridoxine hydrochloride (4a) and 5'
-Deoxy-2',5'-dichloro-3,4'-0-isopropylidenepyridoxine (4b) was quickly prepared from the corresponding dihydroxypyridoxine derivative prior to the coupling reaction to the sulfonamide. Reference Example I N-(2-bromoethyl)-p-)luenesulfonamide 320m of pyridine at 0-5°C! ! To a stirred solution of 2-bromoethylamine hydrobromide (40.0 g, 0.195 mol) in 1.0 g, p-)luenesulfonyl chloride (48.38 g, 0.245 mol; 1.
3 equivalents) were added at a time. TL the reaction every 10 minutes
C (solvent B). 2- that does not contain Her
The absence of bromoethylamine is represented by R,=0 (3
h) after detection by spraying with ninhydrin, pouring the mixture into 2.6β of water containing NaCβ;
Stirred for about 1 hour. The precipitate was collected by filtration and recrystallized from chloroform-cyclohexane.
Obtained 3 g of colorless pieces of 6 (91%): mp 93.5-94.5°C (lit, "mp 88
-90℃); Calculated value (['9)11202Ns8r)
:C, 38,86; H, 4,35; N, 5.04;
S, 11.53; Br, 28.73 Actual value: C, 38,99; H, 4,36; N, 5.01; S
, 11.45; Br, 28.606 varies with reaction temperature and time, but at ambient temperature the reaction mixture contains a significant amount of the corresponding dimer, N-(2-bromoethyl)-N,N '-cytosyl-1,2-ethanediamine was contained. Separating this from 6 is TLC
It was difficult both by crystallization and by recrystallization. Therefore 6
Purity standards were elemental analysis and 'HNMR. Reference Example 2 1.2-ethanediamine derivative (1-3) Method A N,N'-cytosyl-1,
2-ethanediamine (2.0 g) and metallic sodium (0
, 29 g, 2.3 eq.), (refluxed for 1.5 h) and then evaporated the ethanol to DMF (
Disodium N in 55rd. 20 mI of DMF to a suspended mixture of N'-cytosyl-1,2-ethanediamine. N-(2-bromoethyl)-
p-) Luenesulfonamide (6) (3.02 g, 2 equivalents) was added to the solution at about 80° C. and stirred until 6 disappeared. 200m of the reaction mixture! ! of water and the precipitate was collected by filtration. Benzene ethyl acetate (4:1 v/
v), 1.26 g (63%) of starting material N. N'-cytosyl-1,2-ethanediamine and 0.47g
(15%) (R, = 0.3) of compound 1 was obtained, 0.9
g (22%) (Rr = 0.4) of compound 2 was isolated. Compound 1 was recrystallized from ethanol to obtain colorless crystals; mp164-166°C calculated value C25H3+
DgNaSs: C, 53,07; H, 5,52; N,
7.43;S, 17. OO Experimental value c, 52.87; H, 5,58; N, 7.37
;16.96M5: m/z410 (highest value, 1.2%
M+-155 (Ts)) and 184 (100%, CH2
NHTS) IR: 3290 (NH), and 1325 and 1150 (SOz) cm-' Compound 2 was recrystallized from ethanol to obtain colorless crystals; mp193-19
5℃ calculated value C34H4□Cl8N4S4:C,53,
52; H, 5,55; N, 7.34; S, 16.81 Experimental value C, 53,57; H, 5,53; N, ? ,20 ;S
, 16.45 IR: 3290 (NH), and 1325 and 1 15
5 (SOz)am-' Method B (a) N,N'-cytosyl-1,2-ethanediamine (
7,00g'), N-(2-bromoethyl)-p-)
DM of luenesulfonamide (5,813 g, 1.1 eq.) and 7.88 g (3 eq.) anhydrous potassium carbonate
The mixture in 250 rnl of F was stirred at room temperature for 16 hours. The reaction mixture was poured into 2.5 liters of water and the precipitate was collected by filtration. Chloroform-acetone (15:1-12:1-10:
1-85:15 V/V) to give compounds 1.2 and 3 in a ratio of 5:4:1. Compound 3 was recrystallized from chloroform-methanol to obtain colorless crystals; mp166
-167℃ Calculated value C*JsdL. N5Ss; C, 53, 78
;H,5,56;N,? ,29;S,16.70 Experimental value C,53,'64;H,5,53;N,? , 29;
S, 16.58 IR: 3280 (NH), and 1340 and 1 t
55 (SO2)Cm-' (b) Compound 1 (2,03g), N-(2-bromoethyl)-p-)luenesulfonamide (1,09
8 g, 1.1 eq.) and 0.99 g (2 eq.) of anhydrous potassium carbonate in DMF 50 mI! Mixture inside at room temperature
Stirred for 3 hours. After the pretreatment was completed, the residue was subjected to silica gel chromatography and eluted with chloroform-acetone (10: 1-9: lv/v) to obtain compound 1.
(0,5g L 2 (1,7g) and 3 (0,4g)
I got it. N-)Sylated 1,2-ethanediamine derivative (1-3)
and excess anhydrous potassium carbonate (1 for compound 1-3)
4 molar equivalents) of DMF (1.5 g of 1-3/150 mj
! Dichloropyridoxine (4a.b) (1 equivalent ff1) (7) DMF solution (0.5 g of 4
a, b/15 ml of DMF) was added dropwise for 1 hour. Stirring was then continued for 12 hours. The reaction mixture was poured into water containing NaCR. Unless otherwise noted, the precipitate formed was collected by filtration and then purified using silica gel chromatography. Product yield and mp are listed in Table 1. 8a-1
The IR spectra of 0a, 8b-10b and 11-13 are typically 1600.1340 and 1155, and ca.
The band at 380 (C(CL)2) cm-' is characteristic. IR data were described only for bands in the range 900-500c+n-'. Example I N2. N5. N'-)ridosyl-14-hydroxymethyl-14,15'-0-isopropylidene-11
-Methyl-2,5,8-triaza[:9:l (2,5
) Pyridinophane (8a) from the corresponding dihydroxy-6-methylpyridoxine derivative in 50 ml of DMF (4,0
Starting from compound 4a and compound 1 prepared in the presence of 56 g (14 eq.), 1.51 g (94%) of compound 8a was obtained. Colorless crystals were obtained by recrystallization from ethanol; calculated value C3? H440[lN4S3:C,57,5
3; H, 6,10; N, 6.95; S, 11.94 Experimental value: C, 57,33; H, 5,96; N, 6.74; S,
12.13 R, = 0.73 (chloroform-acetone 85:15
v/v) IR:812.745,656,582,576°56
0, and 545 cm"-''HNMR: 1.50 and 1.58 (3H9", C(CH3) respectively
2). 1.8 7 (LH,m, H-C-tI)
. 2.27 (3H, m, CH2). 2.73 (2H, m, CH2). 3, 0 (I H,m, CF(2
). 3.31 (LH, m, CH2). 3.62 and 5.13 (LH, ΔB-q, respectively. J=11.47.pV C(S')dan2N). 3.84 and 4.50 (IH, AB-q, respectively. J = 12.16, pyC(2') 82 N
). 4.78 (2H,s, 2-0 on py-C(4'))
. 2.44.2.64.2.47. and 2.49 (3 each
H, s, A, CH3). 7.31 (4H, m, aromatic boo) 7) and Hif, 37, 7.63, 7.67, and 7.70 (2H, m, respectively)
, d, J=8.05. aromatic proton) MSm/z 613 (31%, M''-155 (Ts
); highest value) Example 2 N2. Ns, NIINI 1-tetratosyl-17
-hydroxy-18-hydroxymethyl-17,18'
-0-inpropylidene-14-methyl-2,5,8,
11-tetraazaC12'] (2,5)-pyridinophane (9a) from the corresponding dihydroxy-6-methylpyridoxine 9-conductor (0,765 g, 1.04 eq.) DMF20
Anhydrous potassium carbonate (5.90 g, 14 eq.) in Ord
Compound 4a and compound 2 (2,326
Starting from g), 2.065 g (70.1%) of compound 9a were isolated. Colorless crystals were obtained by recrystallization from ethanol; Calculated value C46H5SDIONSS4: C, 57,
18; H, 5, 74; N, 7. ．． 25; S, 13.
28 Experimental value: C, 56,92; H, 5,70, N, ? ,i7;S,
13.32 R, = 0.50 (solvent A) IR: 810,760,734,650,572°56
5, and 545 cm-''HNMR: 1.45 and 1.53 (3H, S, C(CH
3)2). 2.33 (3H,s, py-CH3). 2.46.2.45 and 2.48 (3H, 6H, respectively 3H, S, 302 Cs on H4C). 2.05 (LH, m, Cdan 2). 2.25 (LH, m, C dan 2゛). 2.35 (I H, m, CH2). 2.50 (IH, m, Cdan 2). 2.93 (3H, m, CH2). 3.07 (2H,, m, Cdan 2). 3.40 (3H, m, Cdan 2). 3.65 and 4.9'j (IH, ΔB-q, respectively. J=12.33.pY C(2')dan-N). 3.77 and 4.43 (IH, AB-q, respectively. J=13.31.Py C(S')82N). 4.89 and 5.09 (IH, AB-q, respectively. J=11.34.p'IC(4') 20)
. 7.33 (4H, m, aromatic o), and 7.3
°5.7.42.7.67.7.71.7.77 and 7
．． 80 (each 2H, d, J = 8.30. aromatic proton) MS m/z 606 (0.1%, M゛155 (Ts
)-205; highest value) Example 3 NJJJIJ+4-pentatosyl-20-hydroxy-
21-hydroxymethyl-20,21'-〇-impropylidene-17-methyl-2゜5.8.11.14-pentaaza[15:] (2,5)pyridinophane (10
a) DMF20 from the corresponding dihydroxy-6-methyl-pyridoxine derivative (0,698 g, 1.04 eq.)
Compound 4a and compound 3 (prepared in the presence of anhydrous potassium carbonate (5.64 g. 14 eq.) in Ord.
Starting from 2,80 g), 1.58 g (46,6
%) of compound 10a was isolated. Recrystallization from benzene-ethanol gave colorless crystals. Calculated value Cs5Hs60+JgSs: C, 56, 7
8, H, 5,72; N, 7.22. S, 13.78 Experimental value: C, 56,91; H, 5,72; N, 7.15; S, 1
3.66 R, = 0.63 (chloroform-acetone 95:5v/
v) IR:810.740,712,690,655°57
2, and 546 cm""'HNMR: 1.25 and 14.9 (3H, b-s. C(CH3)2, respectively). 2.06 (3H, S, p'l-Cdan,). 2.36.2.38.2.44.2.45. and 2.5
0 (each on 3H,s, 5O2C6H4-C). 2.00.2.40.2.60.3.00. and 3.4
6 (respectively LH, IH, LH, 2H, 3H, m. N-CH2CH2-N). 3.14 and 3.23 (total 38.m. N C82C82N). 3.76 and 4.44 (IH, AB=q. J=12.45.I))l C(S')82 N
). 4.49 and 4.59 (IH, AB-q, respectively. J=14.16.1)yC(2')dan2N). 4.79 and 4.96 (IH, AB-q, respectively. J=15.75.py-C(4′)dan20). MS m/z 578 (0.1%; highest value) Example 4 N', N', N' -)! J) syl-14-hydroxy-15-hydroxymethyl-14,15'-0-
Impropylidene-2,5,8-) Riaza

[9] (2,
5) Pyridinophane (8b) Corresponding dihydroxypyridoxine derivative (0.48g
, 1.35 equivalents) to DMF 150mj! Starting from compound 4b and compound 1 (0.89 g) prepared in the presence of anhydrous potassium carbonate (4.1 g, 14 eq.) in
．． 125 g (95.0%) of compound 8b were obtained. Recrystallization from acetone-ethanol gave colorless crystals. Calculated value C38) 14208N4S3:C,57,2
7, H, 5, 61; N, ? , 42; S, 12.74 Experimental value: C, 57, 37; H, 5, 61; N, ? ,32;S
, 12.75 R, = 0.55 (solvent B) IR: 810.765,755,740,655°58
5.575 and 545 cm-''HNMR: 1.54 and 1.56 (3H,s, C (on C,)2 respectively)
). 1.75.2.34.2.40.2.80.3.12 and 3.30 (each l H, m, N-CH2C82N
). 2.72 (2H, m, N-CH2CH2-N). 2.45 and 2.47 (6H and 3H, s. 302 Cs H4CH3). 3.64 and 4.64 (IH, AB-q, respectively. J=12.45.pyC(5′)dan2-N). 4.00 and 4.89 (lH, AB-q, respectively. J=11.23.PY C(2′)dan2N). 4.90 and 5.14 (LH, AB-q respectively. J=16.84.pY 2-0 on C(4')). and 8.00 (IH, s, py-dan) Example 5 N2. NS, N8. Nl 1-tetratosyl-1
7-hydroxyhydroxymethyl-17.18'-0
-isopropylidene-2,5,8,11-tetraaza-
[12] (2,5) Pyridinophane (9b) Corresponding dihydroxypyridoxine derivative (0,600
g, 1.33 eq) to DMF 150 mI! Starting from Compound 4b and Compound 2 (1,526 g) prepared in the presence of anhydrous potassium carbonate (3,87 g, 14 eq.) in the presence of anhydrous potassium carbonate (3,87 g, 14 eq.), 1.86 g (98%) of Compound 9b was isolated. Recrystallization from benzene-ethanol gave colorless crystals. Calculated value C45Hsso+ oNsSa 'C, 56,
76; H, 5, 61; N, 7.36. S, 13.47 Experimental value: C, 56,66; H, 5,56; N, ? ,33;S
, 13.42 Rr”0.65 (Solvent B) IR:815.740,657,573. and 54
9cm""'HNMR: t, 52 (6H,S,c (cH3)2) 2.45 and 2.47 (4X3H,s. SO□ Cs 84 CH3). 2.62 (5H,b-3,'N-CH2CH2-N
). 2.90 (2H, b-m, N-CH2CH2-N)
. 3.01 (5H, m, N Hz CH2N). 4.07 (2H, b-s, py C(S'
) H2N). 4.33 (2H, b S, pY C(2')H
2-N). 5.04 (2H,S,py C(4')dan, -0),
and 7.82 (LH, s, py-ri) Example 6 N2. NS, N11. Nl 1. N14-Pentatosyl-20-hydroxy-21-hydroxymethyl-20,21'-〇-impropylidene-2.5.8.
11.14-Pentaza[15] (2,,5)pyridinophane (10b) from the corresponding dihydroxypyridoxine derivative (0,152 g, 1.3 eq.) in DMF
Compound 4b and compound 3 (0,5
00g), 0.408g (68%) of compound 10b was isolated. Recrystallization from chloroform-ethanol gave colorless crystals. Calculated value C5db+40+JsSs:C,56,4
2; H, 5,61; N, 7.31. S, 13.95 Experimental value: C, 56,36; H, 5,57; N, 7.20; S,
13.88 R,=0.70 (solvent B) IR:813.739,715,696,657°57
1, and 547 cm-''HNMR: 1.46 (6H,s, C(CH3)2). 2.40.2.41.2.44. and 2.48 (3 each
H, 3H, 6H, 3H, s. 5C)2C6H4CH3). 2,83, and 2.90 (2H, b-t. 2 N'' on C 2 on C). 3.12 and 3.16 (8H, m. N'' CH2C82H5 and N''CH2CH2-N's). 3.25 (4H,m, N' CH2 and CH,-
N”), and 7.78 (LH,s,py second) Example 7 N2. H5,N'-)lidocyl-2,5,8-)reaza

[9] Paracyclophane (11) Anhydrous potassium carbonate (1,93 g, 7
Compound 1 (1,130 g) was mixed with Compound 5 in the presence of
(0,549 g, 1.04 equivalents) to produce 1.
274 g (96%) of compound 11 was obtained by direct recrystallization of the reaction mixture from chloroform-ethanol.
Isolated as colorless crystals. Calculated value C33H3706N3S3: C, 59, 34
; H, 5,59; N, 6.29; S, 14.40 Experimental value: C, 59,24; t-t, 5.51; N, 6.17;
S, 14.36 R, = 0.85 (solvent A) IR: 815.785, 759, 742, 729°65
3.580,560. and 545cm""'HNMR: 2.50.2.60. and 3.10 (6H, IH, and IH, respectively, m, N C82C82N). 2.45 and 2.46 (3H and 6H, s. SO2Cs H, -CH3). 4.24 (4H, b-s. CH2cg H4CH2). 7.34 and 7.67 (4H, d, J = 7.81°N2- and N'-aromatic protons, respectively). 7.29 and 7.65 (2H each, d, J = 7.81°H5-aromatic proton), and 7.40 (4H,s, CC1l H4C) MS m
/z 513 (19%, M"-155 (Ts):
highest value and 133 lowest value) Example 8 N2. NS, H8,Nl 1-tetratosyl-2,
5,8,11-tetraaza(12) valacyclophane (
12)DMF80all! anhydrous potassium carbonate (1,
90g. Compound 2 (1,50 g) was mixed with compound 5 in the presence of
(0.54 g, 1.04 equivalents) to produce 1.
627 g (96%) of compound 12 was obtained by direct recrystallization of the reaction mixture from chloroform-ethanol.
Isolated as colorless crystals. Calculated value C4,H,,O,N4S4: C,58,31;H,5,59;N, 6.49;S
, 14.83 Experimental value: C, 58, 12; H, 5, 52; N, 6.41; S
, 14.80 R, = 0.50 (solvent B) IR: 810,746,732,656,571°56
4, and 546 cm''HNMR: 2.45 (6H,s, N'- and H8-3o□C6H, -CH3'). 2.47 (6H,s, N2- and Nth-8O□C
s H4-CH3). 2.50 (4H, s, H5CH2C mor+-H8>. 2.83 and 2.94 (4H, A282-m, respectively. N2 CH2CH2H5). 4, 14 (4H, s, CH2-C6H
, -C:1-I). 7.33 (4H,s,C-C6H,-C). 7.32 and 7.68 (4H, d, J = 8.30° H5- and H8-aromatic protons, respectively), and 7.37 and 7.78 (4H, d, J = 8.30° N2, respectively) - and N l l - aromatic proton) Example 9 N2. H5,N”,N”,N”-pentatosyl-2,5
,8,11,14-pentaaza [15:] paracyclophane (13) DMF40all! Compound 3 (0,400 g) was reacted with compound 5 (0,132 g, 1.2 eq.) in the presence of anhydrous potassium carbonate (0,400 g, 7 eq.) in 0.5 g.
318 g (96%) of compound 13 was isolated by chromatography. Colorless crystals were obtained by recrystallization from acetone-ethanol. Calculated value Cs+H5sO+oNsSs: C, 57,
66; H, 5,60; N, 6°60; S, 15.09 Experimental value: C, 57,42; H, 5,55; N, 6.45°S,
15.05 R, = 0.8 (solvent B) and 0.4 (benzene-ethyl-acetate 9:1 v/v) IR: 813,740,715,695,657°56
8.546. and 540 cm-''H NMR: 2.44 (3H, s. N3-302 cs H, -CH3). 2.45 (6H, s. H5- and N''S 02 C6N4CH*). 2.47 (6H, s. N2- and N''-3o□C6H4Cdan3). 2.91 and 3.02 (2X2H, t. J=6.59.H5C) [2CH2H8 and H8CH2
CH2N"). 3.07 (2X4H, b s. N2C82C82NS and N" CHz C82N"). 4.26 (4H, s. CH2Cs H4-CH2). 7.32 and 7.59 (2H, d. J respectively = 8.30.N”-aromatic proton). 7.34 and 7.71 (4X2H, d. J=8.30.H5- and NlI-aromatic protons, respectively). Results of the above example are summarized in Table 1. 1st Table 8a 94230d) R@) 93 9a 70126-128 R124 10a 47155-157 R1558b 9523
0-232') R939b 98247-249')
Bf) 12410b 68133-135 F9)
1551296282-284 F 124137
2131-133 F 155a) Yield after purification b) Indicating the presence or absence of rotation of the molecule judged from the signal of the 'HNMR spectrum C) Number of nitrogen atoms contained in the cross-linked chain d) Decomposition e) Constrained rotation f) Boundary g) Free rotation [Effects of the invention] The knowledge obtained in the present invention is extremely important and forms the basis for realizing the object of the present invention. In other words, we have successfully synthesized a molecule that maintains constrained rotation, has sufficient coordination groups in the molecule to incorporate other guest molecules, and is equipped with a functional group that can exhibit the catalytic action of vitamin B6. . In the molecule created by the present invention, the nitrogen functional group is protected by a tosyl group, and the hydroxyl group is protected by an inpropylidene group, but these protecting groups can be easily removed by known methods. Removal of groups; Hamada et al., Journal of the American Chemical Society (J, Am, Chem, Sac, ). ICl3, 140-145 (1986): Removal of isopropylidene group and conversion to functional group similar to vitamin B6; Iwata, Butylene of Chemical Society of Japan (Bull, Chem, Soc. Jpn, ); 14.2835-6 (1981); Iwata et al., same journal, 58.2502-14 (1985)) The significance of the finding that a functional intermediate, which is the key to achieving the object of the present invention, can be synthesized in good yield is This is significant and brings us much closer to creating highly functionalized simple molecules.
It can be said that.

Claims (1)

[Claims] (1) A cyclic polyaza compound represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, Ts is a toluenesulfonyl group, n is an integer from 1 to 3, A is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R represents a hydrogen atom or a lower alkyl group). ] (2) Claim No. (1) expressed by the following general formula
Compounds described in Section. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, Ts is a toluenesulfonyl group, and n is an integer of 1 to 3.) (3) The scope of claim 1 expressed by the following general formula Compound. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, Ts is a toluenesulfonyl group, R is a hydrogen atom or a lower alkyl group, and n is an integer from 1 to 3.) (4) General formula (I): ▲Math. , chemical formulas, tables, etc. ▼ (I) (In the formula, Ts is a toluenesulfonyl group, n represents an integer of 1 to 3.) and the general formula (II): ▲ Numerical formulas, chemical formulas, tables, etc. etc. ▼ [In the formula, X is a halogen atom, A is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (
In the formula, R represents a hydrogen atom or a lower alkyl group. ) is shown. ],
A method for producing a cyclic polyaza compound represented by the following general formula, which comprises performing the reaction in the presence of a dehydrohalogenating agent. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, Ts is a toluenesulfonyl group, n is an integer from 1 to 3, A is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R represents a hydrogen atom or a lower alkyl group). ] (5) The manufacturing method according to claim (4), wherein A is ▲a mathematical formula, a chemical formula, a table, etc.▼. (6) The manufacturing method according to claim (4), wherein A is ▲a mathematical formula, a chemical formula, a table, etc.▼.