Conversion of 11-keto-9-beta, 10-alpha-steroids on 10-alpha-compounds. Synthesis of 10-alpha-cortisone, 11-oxo-10-alpha-progesterone, 10-alpha-androsterone and analogs of 11-hydroxy-compounds

Isomerisation of 11-keto-9β, 10α(retro)-steroids by acid or base led to the thermo-dynamically more stable 11-keto-10α-isomers, which have not yet been described in the literature. This epimerisation at C-9 constitutes a new route for the synthesis of 10α-steroids. The steric factors responsible for this isomerisation are discussed.     

Functionalization of 8-aza-D-homogona-1,3,5(10),13-tetraene-12,17a-diones at positions 11 and 17 under the conditions of the claisen ester condensation. Synthesis and properties of 11- and 17-acylsubstituted 8-aza-d-homogonanes

It was shown that 8-aza-D-homogona-1, 3, 5(10),13-tetraene-12,17a-diones enter into the Claisen ester condensation at the C(₍₁₁₎H₂ and C₁₇H₂ groups, whereas the C₍₁₅₎H₂ group is inert under the investigated conditions. It was established that the direction of the reaction is determined by the structure of the 8-azasteroid substrate. In the presence of a bulky gem-dimethyl group at position 16 the reaction takes place exclusively at the C₁₁H₂ group, while in the absence of this restriction the C₍₁₁₎H₂ and C₍₁₇₎H₂ groups are equivalent. The data from IR, UV, and¹H and¹³C NMR spectroscopy of the initial and synthesized derivatives of 3-aza-D-homogonanes are presented and discussed.Institute of Bioorganic Chemistry, Academy of Sciences of Belarus', Minsk. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 959–965, July, 1995. Original article submitted May 6, 1995.     

Synthesis of dideuterated and enantiomers of monodeuterated tridecanoic acids at C-9 and C-10 positions

We report a route for the preparation of mono and dideuterated tridecanoic acids: (R)-[9-(2)H(1)]-, (S)-[9-(2)H(1)]-, (R)-[10-(2)H(1)]-, (S)-[10-(2)H(1)]-, [9,9-(2)H(2)]-, and [10, 10-(2)H(2)]-tridecanoic acids required as probes for biochemical studies on desaturases. The key intermediates in the synthesis of all these probes are ketones 9, which give rise to the corresponding alcohols 10 and 13 by reduction with LiAlD(4) and LiAlH(4), respectively. Derivatization of nondeuterated racemic alcohols 13 with (S)-(+)-9-anthranylmethoxyacetic acid ((S)-(+)-9-AMA) and chromatographic resolution of both diastereoisomers allowed us to determine the absolute configuration of the stereogenic centers by (1)H NMR using an adaptation of the model proposed by Riguera and co-workers which was validated with alcohols of known absolute configuration. Both enantiomeric alcohols (R)- and (S)-13 were recovered by reduction of each diastereomeric ester with LiAlH(4). Mesylation of alcohols 10 and 13 followed by nucleophilic substitution by LiAlD(4) generated the saturated methoxymethyl derivatives 12 and 16, respectively. Final deprotection and Jones oxidation of the resulting alcohols afforded the above deuterated tridecanoic acids.     

Synthesis of 10-nm scale oligothiophene molecular wires bearing anchor units at both terminal positions

Oligothiophenes with the length of ca.10 nm bearing anchor units (a protected thiol group or trimethylsilylethynyl) at both terminal positions in the conjugated backbone have been synthesized by the block-coupling synthetic strategy. Their electronic properties were clarified by spectroscopic and electrochemical measurements.     

On the effect of Ga and In substitutions in the Ca11Bi10 and Yb11Bi10 bismuthides crystallizing in the tetragonal Ho11Ge10 structure type

The Ga‐ and In‐substituted bismuthides Ca₁₁Ga_xBi_10–x, Ca₁₁In_xBi_10–x, Yb₁₁Ga_xBi_10–x, and Yb₁₁In_xBi_10–x (x < 2) can be readily synthesized employing molten Ga or In metals as fluxes. They crystallize in the tetragonal space group I4/mmm and adopt the Ho₁₁Ge₁₀ structure type (Pearson code tI84; Wyckoff sequence n2 m j h2 e2 d). The structural response to the substitution of Bi with smaller and electron‐poorer In or Ga has been studied by single‐crystal X‐ray diffraction methods for the case of Ca₁₁In_xBi_10–x [x = 1.73 (2); octabismuth undecacalcium diindium]. The refinements show that the In atoms substitute Bi only at the 8h site. The refined interatomic distances show an unconventional – for this structure type – bond‐length distribution within the anionic sublattice. The latter can be viewed as consisting of isolated Bi³⁻ anions and [In₄Bi₈²⁰⁻] clusters for the idealized Ca₁₁In₂Bi₈ model. Formal electron counting and first‐principle calculations show that the peculiar bonding in this compound drives the system toward an electron‐precise state, thereby stabilizing the observed bond‐length pattern.     

Analogs of the dihydroceramide desaturase inhibitor GT11 modified at the amide function: synthesis and biological activities

Dihydroceramide desaturase is the last enzyme in the biosynthesis of ceramide de novo. The cyclopropene-containing sphingolipid GT11 is a competitive inhibitor of dihydroceramide desaturase. The biological effects of chemical modification of the GT11 amide linkage are reported in this article. Either N-methyl substitution or replacement of the amide alpha-carbonyl methylene by oxygen result in inactive compounds. In contrast, both urea (3) and thiourea (4) analogs of GT11, as well as three alpha-ketoamides (5-7), did inhibit the desaturation of N-octanoylsphinganine to N-octanoylsphingosine, although with significantly lower potency than GT11. Furthermore, the alpha-ketoamides 5-7 inhibit the acidic ceramidase with similar potencies (IC50 52-83 microM). Inhibition of the neutral/alkaline ceramidase by these compounds requires around 20-fold higher concentrations. Structure-activity relationships and the biological interest of these compounds are discussed.     

Synthesis and Resolution of 10, 11-Dihydro- 10-hydroxycyproheptadine

10, 11-Dihydro-10-hydroxycyproheptadine was synthesized in a new and facile synthetic route and resolved by L-(-)-2-(1, 3)-dioxo-1, 3-dihydroisoindol-2-yl)-propionic acid and D-( )-tartaric acid, respectively. The free base of the two enantiomers has the same absolute specific rotation value.     

Total synthesis of diastereomeric marine butenolides possessing a syn-aldol subunit at C10 and C11 and the related C11-ketone

Two diastereomeric marine butenolides, (4S,10R,11R)- and (4S,10S,11S)-4,11-dihydroxy-10-methyldodec-2-en-1,4-olide, possessing a syn-aldol subunit at C10 and C11 have been efficiently synthesized by using a three-module coupling strategy. The enantiomeric syn-aldol modules prepared by the syn-selective aldol reaction of the norephedrine-derived chiral propionates were coupled with the chiral C3-C7 module via 1,3-dithiane bisalkylation. The butenolide ring was then installed via a high-yielding ring-closing metathesis (RCM) reaction. Oxidation of the diastereomeric C11-alcohols furnished the corresponding C11-ketones, which are produced by the same marine microorganism.     

Cephalosporins containing carbonate functions at positions 3 and 7

Sulfones of 7-alkoxycarbonyloxy-substituted cephalosporanic acid tert-butyl esters were synthesized by reduction of 7-oxocephalosporanic acid tert-butyl ester, acylation of the intermediate 7-hydroxycephalosporanate with 2,2,2-trichloroethyl chloroformate or di-tert-butyl pyrocarbonate, and oxidation of the sulfur atom. Sulfones of 7-chloro- and 7-alkylidene-substituted 3-alkoxycarbonyloxymethylcephalosporanic acid tert-butyl esters were obtained by replacement of the bromine atom in tert-butyl 3-bromomethylcephalosporanates with hydroxy group and acylation of the latter with chlorocarbonic esters. The cytotoxic activity of the synthesized substances was studied in vitro and also their ability to inhibit elastase.Latvian Institute of Organic Synthesis, Riga LV-1006Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 847–853, June, 2000.     

Synthesis of bicyclopyrroles with various substituents at the bridging positions

Bicyclopyrroles are important synthetic equivalents of isoindoles, which are difficult to synthesize. Using bicyclopyrrole as a starting material, functional organic materials such as benzopyrromethene and benzoporphyrin can be synthesized. However, there are few reports on introducing substituents into bridging positions in bicyclopyrrole. By combining various reactions, we successfully obtained bicyclopyrroles with various substituents at the bridging positions.     

Methylation of the sulfolane ring at the 2 and 2, 5 positions

The possibility of alkylating sulfolane and its derivatives is investigated. A new method of introducing a methyl group at positions 2 and 2, 5 in the sulfolane ring, using sulfolanylmagnesium bromide is put forward.     

Chemistry of modified flavonoids 17. Imidazole analogs of flavonoids

Summary Imidazole analogs of chalcones were synthesized by the reaction of 1-methyl-2 formyl-5-chloroimidazole with o-hydroxyacetophenones. Isomerization and oxidative cyclization of chalcones yielded imidazole analogs of flavonones and flavones. These compounds were used in the synthesis of pyrazolines, pyrazoles, and isoxazoles.Taras Shevchenko Kiev University, Kiev 252017. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1063-1070, August, 1994.For Communication 16 see [1].     

Rapid access to phospholipid analogs using thiol-yne chemistry

Phospholipids and glycolipids constitute an essential part of biological membranes, and are of tremendous fundamental and practical interest. Unfortunately, the preparation of functional phospholipids, or synthetic analogs, is often synthetically challenging. Here we utilize thiol-yne click chemistry methodology to gain access to phospho- and glycolipid analogs. Alkynyl hydrophilic head groups readily photoreact with numerous thiol modified lipid tails to yield the appropriate dithioether phospho- or glycolipids. The resulting structures closely resemble the structure and function of native diacylglycerolipids. Dithioether phosphatidylcholines (PCs) are suitable for forming giant unilamellar vesicles (GUV), which can be used as vessels for cell-free expression systems. The unnatural thioether linkages render the lipids resistant to phospholipase A2 hydrolysis. We utilize the improved stability of these lipids to control the shrinkage of GUVs composed of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and dioleyl-dithioether PC, concentrating encapsulated nanoparticles. We imagine that these readily accessible lipids could find a number of applications as natural lipid substitutes.