Efficient methods have been developed for the synthesis of three potentially useful macroheterocycles containing pyridine-2,6-dicarboxylic and adipic acid ester and hydrazide fragments starting from tetrahydropyran (commercial petrochemical product) through intermediate 8-hydroxyoctan-2-one. The key stages were [2+1]-condensation of the latter with pyridine-2,6-dicarboxylic and adipic acid chlorides and [1+1]-condensation of the resulting α,ω-diketo diesters with dihydrazides derived from the same diacids. The structure of the synthesized compounds was confirmed by IR, NMR, and mass spectra.

A mixture of cyclic lactones [7- (mentholactone), 14-, 21-, 28-, and 35-membered polylactones] instead of the expected [2 + 1]-condensation products was obtained from the reaction of 3R,7-dimethyl-6Shydroxyoctanoic acid, which is accessible from l-menthol, and glutaric, adipic, and bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid dichlorides in Py in the presence of N,N-dimethylaminopyridine. The structures were confirmed using PMR, 13C NMR, and mass spectra.

An optically active macrocyclic diesterdihydrazide with 2,6-pyridinedicarboxylic and adipic acid moieties was synthesized efficiently from available (–)-α-pinene through an intermediate hydroxyketone [1R-(1′-hydroxyethyl)-3R-(2″-hydroxyethyl)-2,2-dimethylcyclobutane) using successive [2 + 1]-reaction of the last with 2,6-pyridinedicarboxylic acid dichloride and [1 + 1]-condensation of the resulting diketodiester with adipic acid dihydrazide.

A one-step synthesis of potentially useful enantiomerically pure macroheterocycles with four esters was developed starting from natural castor oil [(R,Z)-(+)-12-hydroxy-9-octadecenoic acid triglyceride].

Conjugates of betulin and betulinic and betulonic acids with 2-aminoethane- and N-methyl-2-aminoethanesulfonic acids were synthesized for the first time and were interesting as potential biologically active compounds. Experiments in vitro in MDCK cell culture using the MTT assay found that betulin and betulinic-acid derivatives with aminoethanesulfonic acid bound to triterpene C-3 or C-28 through an ester linker were less toxic than the native compounds.

The condensation of 7-oxooctyl 7-oxooctanoate and bis(7-oxooctyl) hexanedioate with bicyclo-[2.2.1]heptane-2- endo ,3- endo -dicarbohydrazide and its 5- endo ,6- endo - and 5- endo ,6- exo -dihydroxy derivatives obtained from dimethyl norbornene-2- endo ,3- endo -dicarboxylate gave the corresponding macrocyclic lactones containing a ketone azine fragment instead of the expected hydrazide moiety.

The cyclization has been studied of N-(2-cyclopent-1-en-1-ylphenyl)benzamides into the corresponding 3,1-benzoxazines by the action of gaseous hydrogen chloride, trifluoroacetic acid, or bromine, and also under conditions of electron impact in the gas phase. A scheme is proposed for the fragmentation of the molecular ions of the products obtained.

Analysis of the electron impact mass spectra, collision-induced dissociation spectra, and high-resolution mass spectrometry data of N-[2-(cyclopent-1-en-1-yl)phenyl]arylamides and isomeric 2-arylspiro[3,1-benzoxazine-4,1'-cyclopentanes] indicated that only a small portion of the molecular ions of the arylamides undergo cyclization to give the corresponding substituted 3,1-benzoxazines prior fragmentation. The donor-acceptor properties of the benzene ring substituents affect the efficiency of cyclization of the molecular ions.

The synthesis of two potentially useful optically active 23- and 30-membered macrolides containing a 1,2-diol system and dihydrazide fragments was developed starting from tetrahydropyran. It was based on [1+1]-condensation of 7-oxooctyl-7-oxooctanoate and bis(7-oxooctyl)hexanedioate with L-(+)-tartaric acid hydrazide.

GC/MS analysis was used to study the thermal stability of 2-arylspiro[3,1-benzoxazine-4,1'-cyclo-pentanes] and isomeric N-[2-cyclopent-1-en-1-yl)phenyl]arylamides. Thermal isomerization of the benzoxazines to give arylamides on the chromatographic column was detected. Change in the ratio between peak intensities of the diagnostic [M]+ and [M-C2H5]+ ions allows to determine the ratio between open and cyclic forms. Heating up to 250°C at atmospheric pressure or prolonged storage of the benzoxazines also leads to their isomerization to arylamides in quantitative yield.

The arrangement of N-[2-(cyclopent-1-en-1-yl)phenyl]benzamide to give 2-phenylarylspiro[3,1-benz-oxazine-4,1'-cyclopentane] was carried out in the presence of DCl. Analysis of the electron impact mass spectra of this benzoxazine and its deuterated analogs showed initial formation of a monodeuterated product. The contributions of polydeuterated benzoxazines increase as the reaction progresses.

Previously unknown seven-membered lactones, (1 R ,1′ R ,5 S ,5′ S )-5,5′-oxybis(1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one), 2,2-dimethyl-1,6-dioxaspiro[2.6]nonan-7-one, 4-(1-hydroxy-1-methylethyl)-7-methyloxepan-2-one, and (4 R ,4′ R ,7 S ,7′ S )-4,4′-[oxybis(propane-2,2-diyl)]bis(7-methyloxepan-2-one), were synthesized by the Baeyer-Villiger reaction using Caro’s acid as a result of oxidative and skeletal transformations of bicyclic monoterpene ketones, (+)-camphor, (+)-nopinone, and (−)-isocaranone.

Eight potentially useful 15-, 17-, 20-, and 22–25-membered macrolides having an azine or hydrazide fragment were synthesized starting from L-menthol, tetrahydropyran, and 4-methyltetrahydropyran via [1 + 1]-condensation of hydrazine hydrate and some dicarboxylic dihydrazides with 7-oxooctyl 7-oxooctanoate, 3-methyl-7-oxooctyl 3-methyl-7-oxooctanoate, and (3 R )-3,7-dimethyl-6-oxooctyl (3 R )-3,7-dimethyl-6-oxooctanoate obtained by the Tishchenko reaction from 7-oxo-, 3-methyl-7-oxo, and (3 R )-3,7-dimethyl-6-oxooctanals, respectively.

A synthesis of optically pure methyl- and isopropyl-branched 21-, 22-, 28-, and 29-membered azinodiesters and diesterdihydrazides from l-menthol using [2 + 1]-condensation of (6R)-8-hydroxy-2,6-dimethyloctan3-one and glutaric and adipic acid chlorides and [1 + 1]-reaction of the intermediate diketodiesters with hydrazine hydrate and glutaric acid dihydrazide was developed.

Potentially useful symmetric macrocyclic diesterdihydrazides were synthesized efficiently from available petrochemical products (tetrahydropyran and 4-methyltetrahydropyran) using successive [2+1]-condensation of 8-hydroxyoctan-2-one and its 6-methyl derivative with glutaric and adipic chlorides and [1+1]-condensation of the intermediate diketodiesters with glutaric dihydrazide.