A. M. Shainurova

Aspects of stereoselectivity in electrophilic addition reactions of iodine with 5-allenyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-1-one and its derivatives

The reactions of 5-allenyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-l-one and related compounds with I2 were studied. The stereochemistry of the resulting 1,2-adducts with I2 at the terminal double bond of the allenic fragment depends in a complex way on the character of functionalization in the cyclopentene fragment of the starting molecule.

Reaction of 5-Allenyl-2,3,5-trichloro-4,4-dimethoxy-2-cyclopentenone and Its Derivative with Iodine

Allenyl-2,3,5-trichloro-4,4-dimethoxy-2-cyclopentenone and 5-allenyl-2,3,5-trichloro-4,4-dimethoxy-1-(2-propynyl)-2-cyclopentenol react with iodine in methylene chloride at room temperature to give the corresponding 5-[(E)-2,3-diiodo-1-propenyl] derivatives.

Prostanoids: LXXXIV. Synthons for New Halochlorvulones II from 6,7-Dichloro-1,4-dioxaspiro[4.4]non-6-en-8-one

By reaction of 6,7-dichloro-1,4-dioxaspiro[4.4]non-6-en-8-one with NaI and LiBr in boiling acetylacetone or methyl butyl ketone the corresponding 3-iodo and 3-bromo derivatives of cyclopentenone were prepared.

Some features of an SmI2−(Me2N)3P—THF system. Transformation of esters into dimethylamides

Smil-intermediates generated upon addition of (Me2N)3P to a solution of SmI2 in THF exhibit the properties of a single-electron reducing agent and an N-nucleophile. In particular,N,N-dimethylamides are formed from esters.

Recyclization of 5-allenyl-2,5-dichloro-3-N,N-dimethylamino-4,4-dimethoxycyclopent-2-enone under the action of SmI2−(Me2N)3P. Functionalizedcis-, trans-cycloocta-2,6-dienones

Reaction of 5-allenyl-2,5-dichloro-3-N,N-dimethylamino-4,4-dimethoxycyclopent-2-enone with Sml2−(Me2N)3P affords new functionalizedcis-,trans-cycloocta-2,6-dienones.

Prostanoids. Part LXIX. Synthesis of (±)-11,15-dideoxy-16-methyl-16-hydroxyprostaglandin E1 ethyl ester

The first prostaglandin preparation with antisecretory type of action, created by the Searle Company on the basis of compound I (misoprostol), has been successfully used for a long time in medicinal practice for preventing stomach ulceration during the administration of nonsteroidal antiinflammatory drugs [ 2 6 ] . As is seen from the diagram of the structure, misoprostol is an analog of natural pmstaglandin El (PGEI, compound II) with an OH group shifted from C 15 to C 16 and an additional methyl group. This modification, not affecting the gastro-antisecretory properties of the initial compound, markedly reduced the side effects and increased the stability of misoprostol with respect to metabolism [7]. Although it was reported that only the enantiomer of I with the natural (11R, 16S) configuration of chiral centers is active [6], the drug misoprostol used in practice represents a racemic 1 : 1 mixture of two Clr-epimers. This is explained both by the absence of any significant side effects caused by the other isomers, the possible mutual transformation of isomers I with tertiary alcohol groups in an acid medium (in the stomach), and by serious technological difficulties in the enantioselective approach to 16S-I [5]. In beginning work in this direction, we paid attention to the fact that a potentially more readily accessible I 1-deoxy analog (Ili) 3 of misoprostol had not been reported even though the antisecretory activity of l l-deoxy-PGEl was known to be comparable to the activity of the natural PGEI [9, 10]. At the same time, it was stated with confidence [1 I]

Prostanoids. Part LXXIV. Antiulcerous activity of misoprostol and its 11-deoxy analog. Misoprostol synthesis

Ermisoprostol (I), a racemic analog of the natural prostaglandin is successfully used in medical practice for preventing stomach ulceration during the administration of nonsteroidal antiintlammatory drugs [1, 2]. In the previous communication [3], we showed good prospects for the search of new antiulcerous agents in the series of readily accessible 11deoxy-modified analogs of compound I and reported on the synthesis of compound II representing this series.

(±)-2,3,5-trichloro-4,4-ethylenedioxycyclopent-2-en-1-one and its 5-allyl-substituted derivative in conjugated 1,4-addition with dimethyldilithium cyanocuprate

Abstract(±)-2,3,5-Trichloro-4,4-ethylenedioxycyclopent-2-en-1-one reacts with Me2CuCNLi2 to give depending on conditions the corresponding 3-methyl substituted cyclopentenone (AdNE adduct) or a mixture of unsaturated acyclic acids formed as the result of abnormal cleavage reaction of C(1)−C(2) bond in the trichorocyclopentenone. Reactions of conjugated 1,4-addition of Me2CuCNLi2 to (±)-5-allyl-2,3,5-trichloto-4,4-dimethoxycyclopent-2-en-1-one lead to products of replacement of vinylic Cl atom at C(3) by Me group and those of C(5)-dechlorination.

INTERACTION OF DIMETHYLSULFOXONIUM METHYLIDE WITH 5-ALLYL-2,3,5-TRICHLORO-4,4-DIMETHOXYCYCLOPENT-2-EN-1-ONE

Dimethylsulfoxonium methylide in DMSO initiates unusual oxidative skeletal transformations of trichlorocyclopentenone. Lactone, cyclic orthoester, and a number of by-products of hydrolysis, substitution, and reduction were isolated and characterized. The expected epoxide was obtained in low yield.