Eiji Imai

Novel reactions of 1-benzoyl-2-methyl-3,4-dihydro-2-thianaphthalene with compounds having an acidic hydrogen

Thermal reaction of 1-benzoyl-2-methyl-3,4-dihydro-2-thianaphthalene (1) with acids or thiols in benzene afforded ring-opened products cleaving C1-S bond. On the other hand, ring-expanded product was produced by the reaction of 1 with imides or phenols.

(1,2-diphenylethyl) piperazines as potent opiate-like analgesics; The unusual relationships between stereoselectivity and affinity to opioid receptor

A series of novel diphenylethylpiperazines were synthesized, and analgesic activities and opioid receptor interactions were evaluated. Analgesic activity of S(+) enantiomer of 1-cyclohexyl analogues (I-C6) was as potent as morphine. This compound showed narcotic properties. Racemate of I-C6 demonstrated the most potent analgesic activities among the enantiomorphic pairs. The R(-) isomer and (-) spa, NN-dimethyl-1, 2-diphenylethylamine, had mu-agonist like character. The S(+) isomer possessed high affinity for all types of the receptor, especially favorable for delta and kappa, in the different manner from opiate-like analgesics. It is conceivable that opioid receptor has various subsites, and this S(+) enantiomer alter the conformation of the receptor.

Novel ring transformation reactions of xanthine derivatives

Abstract The novel ring transformation reactions were found in the reactions of 1,3,7,9-tetra-alkyl-8,9-dihydroxanthines and acetylenic compounds. The reaction of the dihydroxanthine with DMAD gave a propellane type compound and with methyl propiolate afforded the similar type compound and a pyrimido[4,5-b]diazepine derivative. The mechanism of these reactions was also discussed.

An unexpected double cycloaddition of [1,2,4]triazolo[1,5-a]pyrimidine N-ylide with activated acetylenes and alkenes

The reaction of 5,7-dmethyl-[1,2,4]triazolo[1,5-a]pyrimidinio-3-phenacylide (5) with activated acetylenes gave 1 : 2 adducts of ylide–R–CC–R. The structures of the products were determined as 3,3a-dihydropyrazolo[1,5-c]pyrimidine derivatives (7) by hydrolysis, 1H and 13C n.m.r., and X-ray crystallography. Molecular orbital calculations (ab initio) of the model compounds were performed in order to elucidate the mechanism for the formation of the 1 : 2 adducts. The results of the calculations suggested that an intermediate, 1 : 1 adduct would be less reactive than the starting ylide. However, despite many attempts isolation of the 1 : 1 adduct was unsuccessful. The 1 : 2 adduct was obtained even from the reaction of the ylide with 0.5 equiv. of the acetylenic compound. Easy formation of the 1 : 2 adducts can be explained by an equilibrium between the 1 : 1 adducts and the starting materials.

CHEMICAL FEATURES FOR OPIATE AGONIST AND ANTAGONIST

Summary We synthesized novel tetracyclic benzomorphan derivative, (5R*, 5aS*, 6R*, 7R*, 11bR*)-5,7-ethano-4,5,5a,6, 7,11-hexahydro-2,6,7-trimethyl-1H-benzo[g]homoquinolin-9-o1 (A) in which N-dimethylallyl substituent of pentazocine was cyclized to B ring. (A) could show only antagonistic property on Snyders conception and only agonistic property on Kolbs model. Thus, its dihydro compound (B) and related 6-membered ring compounds (C and D) were obtained to examine effects of unsaturated bond and size of the newly constructed ring. Although analgesic activities and opiate receptor bindings of both (A) and (B) were slightly weaker than those of pentazocine, these compounds had no antagonistic property

Reactions of xanthinium N(7)-ylides with olefinic dipolarophiles

The stereo- and regio-chemical aspects of the reactions of xanthinium N(7)-methylides (2) with olefinic dipolarophiles were elucidated. The reactions of ylides (2) with N-phenylmaleimide afforded stereoselective endo adducts, and with acrylates and acrylonitrile afforded stereo- and regio-selective 6-endo adducts. On the other hand, the reactions of ylides (2) with trans-olefins afforded mixtures of two stereoisomers, the 8-endo-7-exo and 8-exo-7-endo pyrrolo[2,1-f]purine derivatives. Stereochemistry of the adducts was elucidated by 1H n.m.r. and X-ray analysis. The stereoselectivity of the adducts was governed by the balance of steric and electronic effects. The ylides (2) reacted in their Z-form in all reactions investigated. The steric factors of the dipolarophiles were also closely examined.

Generation of [1,2,4]triazolo[1,5-a]pyrimidine N-ylides and their ring transformation reactions

[1,2,4]Triazolo[1,5-a] pyrimidine (1) has been alkylated at the N(3)-position by treatment with alkyl halides in refluxing dry acetone. The ylides (3) were generated in situ from the iminium salts (2) and 1 equiv. of triethylamine. Thermolysis of the ylides (3) in dry acetonitrile gave the 2-cyanamido-pyrimidines (4). The N(3)-phenylacyliminium salt (2e) when treated with 2 equiv. of triethylamine gave 2-(2-imino-5-phenyl-2,3-dihydro-oxazol-3-yl)pyrimidine (5) in 64.4% yield. The latter on hydrolysis gave the oxazolone (7), and on treatment with nucleophiles such as alcohols or amines under acidic conditions afforded the ring transposition products imidazol-2-ylpyrimidines (8) or (9), respectively. The reaction mechanism for the novel thermolysis of the ylides is discussed.

Thermal reactions of 2-alkyl (or aryl)-1-benzoyl-3,4-dihydro-1H-2-thionianaphthalen-1-ides with compounds possessing an acidic hydrogen

Thermal reactions of 2-alkyl-1-benzoyl-3,4-dihydro-1H-2-thionianaphthalen-1-ides (1a–d) in ethanol afforded alkyl o-vinylbenzyl sulphides (2a–d) along with ethyl benzoate, whereas that of the 2-phenyl congener (1e) gave o-(ethoxymethyl)phenethyl phenyl sulphide (3) together with the sulphide (2e). The ylides (1a and e) reacted with boiling water to afford the benzoates (9a and e). Reactions of the ylides (1a–e) with carboxylic acids and thiols gave the ring-opening products (11)–(17), cleaving the C(1)–S bond. Reactions of the ylide (1a) with succinimide or phthalimide yielded the ring-expansion product 2-phenyl-4,5-dihydro-3,5-benzoxathionine (19). In the reaction of the ylide (1a) with phenol, the product proportions changed with amounts of phenol. When 2 equiv. of phenol were used, the oxathionine (19) was obtained. However, the ring-opening products (22) and (23) were formed by using 10 or 100 equiv. of phenol.These reactions are initiated by protonation on the ylidic carbanion to form the sulphonium salt (5). The conjugate base formed concurrently attacks a different reaction site, viz. a carbonyl carbon, C(1), or a methyl proton of the sulphonium salt (5), depending on its character.

CYCLOADDITION REACTIONS OF XANTHINIUM N(7)-YLIDES WITH TRANS OLEFINIC DIPOLAROPHILES

Cycloadditions de xanthinyliomethanures-7: obtention de pyrrolo [1,2-f] xanthines; selon les composes de depart, obtention des produits endo et/ou exo

A ROLE OF LIPID IN OPIATE-RECEPTOR INTERACTION

The interaction between opiates and lipids vesicle was studied by fluoripolarimetric method to examine a rotational freedom of bound opiates using the intrinsec fluorescence of opiates. Among the selected combinations of the lipid-opiate system tested, phosphatidyl inositol showed the highest affinity to morphine and its analogues, resulting in a strong immobilization of bound opiates, whereas the other phospholipids and cerebroside sulfate did not alter the dynamic property of the opiates even certain interaction was expected from the change in fluorescence intensity. Phosphatidyl serine which quenched the opiate fluorescence, also showed a slight immobilization of some opiates. On the contrary, the endogenous opioids were not immobilized even by phosphatidyl inositol.