Roman L. Wydra

Structure-activity relationship studies of CNS agents. Part 29. N-Methylpiperazino-substituted derivatives of quinazoline, phthalazine and quinoline as novel α1, 5-HT1A and 5-HT2A receptor ligands

Summary New N -methylpiperazino-substituted quinazolines 8 and 9 , phthalazine 13 , and quinoline 19 have been synthesized. The receptor binding profiles (α 1 , 5-HT 1A , 5-HT 2A ) of these compounds and their analogs ( 7–22 ) have been determined. It has been demonstrated that orientation of a local dipole moment of the heteroaromatic ring system affects both the α 1 and 5-HT 2A affinity of the investigated class of ligands. Distortion of the coplanar unfused heteroaromatic ring system results in a decreased 5-HT 2A affinity. 4-(4-Methylpiperazino)-2-(2-thienyl)quinoline 18 is the most active and selective α 1 ligand ( K i = 4.9 nM) with a much lower affinity for 5-HT 1A ( K i = 3420 nM) and 5-HT 2A ( K i = 211 nM) receptors.

Reaction of some trisubstituted steroid epoxides with triphenylphosphine - iodine complex. Deoxygenation of epoxides

Abstract Triphenylphosphine - iodine complex was found to be an effective reagent for deoxygenation of trisubstituted steroidal epoxides. The mechanism of the reaction is proposed.

A Novel Route to 7-(Substituted Amino)-5,6-dihydrobenz[c]acridines

The title compounds (3) are produced in a novel, lithium alkylamide- and dialkylamide-mediated cyclization of N-(1,2,3,4-tetrahydro-1-naphthylidene)-2-trifluoromethylaniline (2). The mechanism of this unusual transformation that involves the trifluoromethyl group is discussed

A NOVEL SYNTHETIC ROUTE TO 1,3-DISUBSTITUTED NAPHTHALENES

Abstract 1-(2-Substituted 1-propenyl)-2-(trifluoromethyl)benzenes are cyclized to 3-substituted 1-(4-methylpiperazino)naphthalenes in a lithium 4-methylpiperazide-mediated reaction that involves the trifluoromethyl group.

Highly stereoselective rearrangement of (E,E)-suspensolide to anastrephin and epianastrephin

Abstract The facility of the title rearrangement has clear mechanistic implications for the major pathway in the biosynthetic production of anastrephin ( 2 ) and epianastrephin ( 3 ) in the male Anastrepha fruit fly species A. suspensa (Caribbean) and A. ludens (Mexican).

Conformational analysis of 4,8-dimethyl-3(E),8(E)-decadien-10-olide (E,E-suspensolide), a key component of the pheromones of the male caribbean and mexican fruit flies

Abstract Molecular modeling and NMR studies of suspensolide (1), a major component of the sex and aggregation pheromones of the Caribbean, A. suspensa [Loew], and Mexican, A. ludens [Loew], fruit flies reveal two major conformers with the methyls syn.

Addition and lithiation reactions of N-(1-phenylalkylidene)anilines with lithium dialkylamides

Abstract Lithium diisopropylamide undergoes an addition reaction to the methyleneamino moiety of the title Schiffs bases substituted with a cyano group at the ortho or para position of the aniline, but mediates tautomerization of the unsubstituted and meta -substituted derivatives into secondary enamines. Only the tautomerization is observed for lithium 2,2,6,6-tetramethylpiperidide-mediated reactions.

CHEMISTRY OF THE ANIONICALLY ACTIVATED PERFLUOROALKYL GROUP IN HETEROCYCLIC SYNTHESIS

One-pot reactions of 2-(perfluoroalkyl)anilines 1 and 2 with the corresponding heteroaryllithium reagents provide facile synthetic entries into heteroaryl-substituted methanes 9 ,11,13, fused quinolines 10, and quinolines 14-17. In a similar fashion, 2-(trifluoromethyt)benzyl chloride (3) is a building block for the construction of fused tetracyclic systems of thiophene, furan, and AAmethylpyrrole 18-20. Potassium terf-butoxide-mediated selfcondensation of [2-(trifluoromethyl)phenyl]acetonitrile (4) yields a substituted naphthalene 21, the 2-amino-1-cyano functionality of which may serve as a building block for fused pyrimidines. The high reactivity of orthoand para-(perfluoroalkyl)anilines, such as 1,2, and a high stability of their meta isomers under basic conditions are well understood (1). Briefly, as illustrated in Scheme 1, the anion 5 derived from 1 or 2 undergoes elimination of fluoride ion from a benzylic position, and then the resultant non-aromatic intermediate product 6 is aromatized by the addition reaction with a nucleophile to generate 7. The subsequent steps depend on the nature of the nucleophilic species and may include an analogous elimination/addition pathway and/or cyclization with the involvement of the ortho amino group. Facile synthetic entries to diverse classes of heterocyclic, carbocyclic, and acyclic classes of compounds by using this mechanism-based approach have been developed (1-4). Yet, in this paper we report new applications of 1 and 2 in heterocyclic synthesis. We also describe a novel chemistry of 2-(trifluoromethy)benzyl chloride (3) and [2-(trifluoromethyl)phenyl]acetonitrile (4) under basic conditions (5). Scheme 1 1: Rf = F, X = NH 2: Rf = C3F7, X = NH 3: Rf = F, X = CHC1 4: Rf = F, X = CHCN 5 6 7