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New di-, tri-, tetra-, and pentanorlabdane compounds with thiosemicarbazone and 1,3-thiazole fragments were synthesized. Their antifungal and antibacterial activities were studied. The main advantages of this research were the available starting material, i.e., the natural labdane diterpenoid (–)-sclareol, which was isolated from renewable resources, and the high probability of biological activity combined with the low toxicity of these compounds because of their natural origin.

Series of drimane and homodrimane sesquiterpenoids with oxadiazole and thiadiazole fragments were synthesized. Their antifungal and antibacterial activities were studied.

Using sclareol and sclareolide as starting materials, the guanidine derivatives of 12-amino-11-dihomodrimane-8α-ol and 13-amino-14,15-bis-dinorlabd-8(9)-ene were synthesized by the reaction of the corresponding amines with sodium hydrogencyanamide in ethanol – water solution. Monoacyl- and diacylguanidines were prepared from activated with N,N-carbonyldiimidazole Δ8,9-bicyclohomofarnesenoic acid by the reaction with guanidine. Their structures were confirmed by the 1H and 13C NMR, IR spectral and elemental analysis data. The compounds 12, 13 and 15 were screened for their antiproliferative and cytotoxicity activities against Colo 205, Colo 320 and MRC 5 human lung fibroblasts with respect to standard drug, Cisplatin. The compounds 12 and 15 exhibits excellent results than positive control. Hence these two compounds may be act as drug lead molecules in cancer chemotherapy.

Drimenic acid was synthesized in six steps from norambreinolide. Reaction of drimenic acid with oxalyl chloride produced iso-drimenic acid chloride, which reacted with heterocyclic amines (2-aminopyrimidine, 2-aminopyrazine, 4-aminopyrimidine, N-aminocarbazole, and 3-amino-1,2,4-triazole) to form amides of iso-drimenic and albicanic acids. The structures of the amides were elucidated by spectral methods and an X-ray structure analysis.

12,12′-Azino-di-8′-hydroxy-11-dihomodrimane, N,N′-di-(8′-hydroxy-11-dihomodrim-12-ylidene)-adipic acid dihydrazide, N,N′-di-(∆8,13-bicyclohomofarnesenoyl)-hydrazine, and hydrazides of ∆8,9- and ∆8,13-bicyclohomofarnesenoic acids were synthesized.

Amides of ∆ 8,13 -bicyclohomofarnesoic acid containing 1,2,4-triazole and carbazole rings were synthesized in eight steps from commercially available norambreinolide. The compounds were prepared by reacting the acid chloride with the heterocyclic amines 3-amino-1,2,4-triazole and N-aminocarbazole. Their structures were elucidated by spectral methods and x-ray crystal structure analyses.

A series of dihomodrimane sesquiterpenoids containing an NH2 group were synthesized. 11-Dihomodriman-8α-ol-12-one and its dehydration products, ketones with double bonds in the C7-C8 and C8-C9 positions, were prepared from commercially available norambreinolide. The oximes of the ketones were reduced by LiAlH4 to the corresponding amines.

Herein we report a feasible study concerning the design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton. The reaction pathway is efficient and straight, involving the direct N-acylation of diazine with homodrimane sesquiterpenoids bearing acyl chlorides or organic acids functionality. A reliable explication and a feasible reaction mechanism for the obtained compounds are presented. The in vitro antimicrobial activity of the homodrimane sesquiterpenoids with and without diazine skeleton has been evaluated. All the tested compounds have an excellent antibacterial activity against Gram-positive strains S. aureus and B. cereus. SAR correlations concerning antimicrobial activity are reported. The design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton are described. Antimicrobial tests prove that some homodrimane sesquiterpenoids have an excellent biological activity.

A comprehensive study of the synthesis and structure of new homodrimane sesquiterpenoids with diazine skeleton is presented. This is the first synthesis of homodrimane sesquiterpenoids with diazine skeleton. In the same time, an efficient way for the one-pot bisacylation of 2-aminopyrimidine is reported. The structure of the bisacylamide was proven unambiguously, including the single-crystal X-ray structure determination. A reliable explication and feasible reaction mechanisms for the obtained compounds are presented.

Products from the reaction of 11-dihomodriman-8α-ol-12-one with several reagents such as MeSO3SiMe3, CF3SO3SiMe3, Sc(CF3SO3)3, conc. H2SO4 in EtOH (30% solution), and Amberlist-15 ion-exchange resin were studied. 11-Dihomodrim-8(9)-en-12-one and its oxime were synthesized. The reaction of its oxime with H3PO4 (86%) or CF3CO2H produced (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho [1,2-e]-3-methyl-4,5-dihydro-[1,2,6]-oxazine; with p-TsCl in Py, (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1,2-d]-2-methylpyrroline-N-oxide; and with PCl5 in Et2O, 11-acetylaminodrim-8(9)-ene and 11-methylaminooxodrim-8(9)-ene.

13-Amino-14,15-dinorlabd-8(9)-ene was synthesized from sclareol in four steps in 47% total yield. 14,15-Dinorlabd-8(9)-en-13-one was an intermediate compound, reduction of its oxime with LiAlH4 was a key step of this synthetic scheme.

Beckmann reaction products of 11-dihomodriman-8α-ol-12-one oxime with Ac2O in pyridine, 86% H3PO4, p-TsCl in pyridine, and PCl5 in ether were investigated. It has been found that the major product from treatment of the oxime with Ac2O is the oxime acetate. Reaction of the oxime with 86% H3PO4 gave (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1, 2][5, 6]-3-methyl-4,5-dihydro[1, 2, 6]oxazine; with p-TsCl, (1S,2S,4aS,8aS)-2,5,5,8a-tetramethyldecahydro-1H-naphtho[1, 2][5, 6]-2-methyl-4,5dihydro[1, 3, 6]oxazine; with PCl5, a mixture of products containing 11-acetylamino- and 11-methylaminooxodrimenes that were isomeric at the double bond, norambreinolide, and a 1,3,6-oxazine.

11-Aminodrim-7-ene was synthesized from drimenol in four steps. Drimenol was oxidized into drimenal and its oxime was dehydrated by p-tosylchloride or acetic anhydride in pyridine to form 9-cyano-11-nordrim-7-ene, reduction of which by LiAlH4 in the presence of anhydrous AlCl3 produced 11-aminodrim-7-ene. The reaction of 9-cyano-11-nordrim-7-ene, NaBH4, and CoCl2·6H2O produced a mixture of drimenylamine and 7,8-dihydrodrimenylamine in a 2:1 ratio.

The dehydration products of driman-8α,11-diol-11-monoacetate that are formed upon reaction with several dehydrating agents and the products from elimination of the C-8 acetoxy group in driman-8α,11-diol diacetate were investigated in detail. A new effective synthesis of drimenylacetate from driman-8α, 11-diol-11-monoacetate by its regioselective dehydration using methanesulfonic acid trimethylsilyl ether was developed.

Drim-9(11)-en-8α-ol and drim-9(11)-en-8β-ol were synthesized in six steps from drimenol. Drimenol was oxidized by P2O5 and DMSO to drimenal, which isomerized with p-TsOH into isodrimenal. Isodrimenal was reduced by NaBH4 into isodrimenol, epoxidation of which by m-CPBA gave a mixture (3.4:1) of α- and β-epoxyisodrimenols. These reacted with tosyl chloride in Py to give a mixture of α- and β-epoxyisodrimenol tosylates. Treatment of the tosylate mixture with KI and then Ph3P produced a mixture of drim-9(11)-en-8α- and -8β-ols that was separated chromatographically. The overall yield was ∼26%.

A convenient synthesis of drimenol by treatment of readily available drimane-8α, 11-diol 11-monoacetate with sulfuric acid in ethanol under mild conditions was developed. Oxidation of drimenol with selenium dioxide gives known drim-7-ene-9α, 11-diol and drim-7-ene-11,12-diol as the major products.

An efficient one-step synthesis of the diacetate of the tetracyclic triterpenoid onoceranediol (4) by radical cleavage of the readily available 12-hydroperoxy-8α,12-epoxy-11-bishomodrimane is described. Drim-9(11)-en-8α-yl acetate (7) is formed in this reaction as a byproduct. Onoceranediol diacetate 4 is converted into onoceranediol on treatment with LiAlH4, and acetate 7 is transformed into drim-9(11)-en-8α-ol on saponification.

Reaction of 4-(2-, 3-, 4-pyridyl, or 2-quinolyl)but-3-en-2-ones with carbethoxymethylenetriphenylphosphorane and subsequent hydrolysis gives 3-methyl-5-(2-, 3-, 4-pyridyl, or 2-quinolyl)-2,4-pentadienoic acids and also 3-methyl-4-(2-, 4-pyridyl-, or 2-quinolylmethyl)but-2-en-4-olides as products of cyclization of the corresponding pentadienoic acids.

A simple, efficient two-step synthesis of a mixture of diethyl (Z) and (E)-3-methylglutaconates from ethyl 4,6-dimethyl-2-oxo pyran-5-carboxylate in 83% yield is described. On the basis of this synthesis an improved procedure for the preparation of a mixture of (Z)- and (E)-3-methylglutaconic acids from ethyl acetoacetate in 44% overall yield was elaborated

Reaction of 4-(2-, 3-, 4-pyridyl, or 2-quinolyl)but-3-en-2-ones with carbethoxymethylenetriphenylphosphorane and subsequent hydrolysis gives 3-methyl-5-(2-, 3-, 4-pyridyl, or 2-quinolyl)-2,4-pentadienoic acids and also 3-methyl-4-(2-, 4-pyridyl-, or 2-quinolylmethyl)but-2-en-4-olides as products of cyclization of the corresponding pentadienoic acids.

A simple, efficient two-step synthesis of a mixture of diethyl (Z) and (E)-3-methylglutaconates from ethyl 4,6-dimethyl-2-oxo pyran-5-carboxylate in 83% yield is described. On the basis of this synthesis an improved procedure for the preparation of a mixture of (Z)- and (E)-3-methylglutaconic acids from ethyl acetoacetate in 44% overall yield was elaborated