Yuefei Hu

Synthesis of chiral ligands derived from the Betti base and their use in the enantioselective addition of diethylzinc to aromatic aldehydes

Abstract A novel procedure for selective direct N , N -alkylation of the chiral Betti base was developed, and a new family of chiral ligands, ( S )-1-(α-cycloaminobenzyl)-2-naphthols, were prepared. The ligands with five- and six-membered cyclic amines showed highly efficient asymmetric induction in the addition of diethylzinc to aromatic aldehydes in 93–96% yields and 91–99% ee.

Novel preparation of non-racemic 1-[α-(1-azacycloalkyl)benzyl]-2-naphthols from Betti base and their application as chiral ligands in the asymmetric addition of diethylzinc to aryl aldehydes

A novel route for the preparation of non-racemic 1-[α-(1-azacycloalkyl)benzyl]-2-naphthols was developed, which involves regioselective N-cycloalkylation of the Betti base with dials in the presence of NaBH3CN to give 1-azacycloalka[2,1-b]oxazine followed by the selective cleavage of a C–O bond with LiAlH4. As a new family of chiral ligands, their application in the enantioselective addition of diethylzinc to aryl aldehydes was tested. The ligands incorporating pyrrolidine and piperidine led to highly efficient asymmetric induction to give products in up to 96% yield and 99% ee.

The Aromatization of Hantzsch 1,4-Dihydropyridines by Tetrakis-Pyridine Cobalt (II) Dichromate (TPCD)

Abstract Aromatization of Hantzsch 1,4-dihydropyridines (la-n) were promoted by tetrakis-pyridine cobalt (11) dichromate to yield corresponding pyridine derivatives (2a-n) in moderate to high yields (70-87%). The reaction was carried out under mild and convenient conditions.

Neurosteroid analogues. Part 5.1 Enantiomers of neuroactive steroids and benz[e]indenes: total synthesis, electrophysiological effects on GABAA receptor function and anesthetic actions in tadpoles

The synthesis of (3β,5β,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one 2, (3β,5β,8α,9β,10α,13α,14β,17α)-3-hydroxyandrostane-17-carbonitrile 4,† [3R-(3α,3aα,5aβ,7α,9aα,9bβ)]-1-[dodecahydro-7-(2-hydroxyethyl)-3a-methyl-1H-benz[e]inden-3-yl]ethanone 6 and [3R-(3α,3aα,5aβ,7α,9aα,9bβ)]-dodecahydro-7-(2-hydroxyethyl)-3a-methyl-1H-benz[e]indene-3-carbonitrile 8 is reported.‡ Steroids 2 and 4 have been used previously to investigate the enantioselectivity of steroid action on GABAA receptor function and to correlate steroid action at this receptor with the anesthetic actions of the compounds. The enantioselective actions of benz[e]indenes 6 and 8 have been evaluated for the same reasons in this study. Similar correlations between the enantioselective effects of both classes of compounds on GABAA receptor function and anesthetic potency in tadpoles have been observed.

A Versatile Oxidizing Agent: Tetrakis-pyridino-cobalt(II) Dichromate Py4Co(HCrO4)2 (TPCD). Oxidations of Alcohols, Halides and Amines to Their Corresponding Carbonyl Compounds

Abstract The preparation of a versatile oxidizing agent tetrakis-pyridino-cobalt (II) dichromate Py4Co(HCrO4)2 (TPCD) is presented and its structure is confirmed by x-ray crystal data. Alcohols, halides and amines are oxidized smoothly to their corresponding carbonyl compounds in good yields with TPCD.

CuI catalyzed N-arylation of amide as a key step for the preparation of 3-aryl β-carbolin-1-ones

An expedient synthetic route for 3-aryl beta-carbolin-1-ones was developed starting from ethyl acetamidocyanoacetate and chalcone derivatives. The five- and six-membered nitrogen-containing rings in the beta-carbolin-1-ones were elaborated efficiently by an intramolecular ketone-nitrile annulation and an intramolecular N-arylation of amide respectively.

Synthesis of (5α)-17-azaandrostan-3-ols and (5α)-17-aza-D-homoandrostan-3-ols and their N-acylated derivatives

Two groups of N-acylated D-azasteroids (4 and 5) were synthesized to explore structure-activity relationships for steroid modulation of GABA(A) receptor function. The target compounds were prepared conveniently from (5alpha)-3-hydroxyandrostan-17-ones (6 and 7) via the intermediate (5alpha)-17-aza-D-homoandrostan-3-ols (14 and 15) or (5alpha)-17-azaandrostan-3-ols (18 and 19) precursors in high overall yields. A Beckmann rearrangement and a Hofmann rearrangement were employed as two key steps in the synthetic sequences.

Synthesis of 1,10-seco-5α-estr-1 -ynes: potential mechanism-based inhibitors of 3α- and 3β-hydroxysteroid dehydrogenases

Oxido-reductase reactions mediated by 3α- and 3β-hydroxysteroid dehydrogenases alter the biological effects of steroid hormones. A novel and practical synthetic route from 19-nortestosterone 1 to (3R,S)-1,10-seco-5α-estr-1-yne-3,17β-diol 13a and structurally related analogues has been developed so that the potential of these 1,10-secosteroids as mechanism-based inhibitors of 3α- and 3β-hydroxysteroid dehydrogenases can be evaluated. Following double-bond reduction and acetylation of steroid 1, the Δ2-enol tert-butyldimethylsilyl ether derivative 4 is formed with high regioselectivity, then cleaved by ozonolysis, reduced with NaBH4, and methylated with CH2N2 to give 2,3-secosteroid 6. Carbons C1 and C2 are then sequentially removed to yield the (dodecahydro1H-benz[e]inden-7-yl)acetic acid derivative 10. Partial reduction and deacetylation of compound 10 by DIBALH yields the (dodecahydro-1H-benz[e]inden-7-yl)acetaldehyde derivative 11. The addition of HCCMgBr, LiCCCl and LiCCCF3 to aldehyde 11 yields 1,10-seco-5α-estr-1-yne 13a, and the chloro- and trifluoro-methylacetylenic analogues 13b and 13c, respectively. Selective oxidation by DDQ of 13a, and 13b, but not 13c, yields the corresponding 3-keto-1,10-secosteroids 14a and 14b.

A Facile Preparation of 1,2,3-Triaroylindolizines

Abstract Fourteen 1,2,3-triaroylindolizines were prepared conveniently by oxidation of corresponding N-aracyl pyridinium or substituted pyridinium bromides with a versatile oxidant TPCD [(Py4Co(HCrO4)2, tetrakis-pyridino-cobalt (II) dichromate] in 12–42 % yields.

Preparation of (5α, 13α)-D-azasteroids as key precursors of a new family of potential GABAA receptor modulators

Abstract Three groups of (5α,13α)- d -azasteroids, (5α,13α)-3-hydroxy-17a-aza- d -homoandrostans ( 12 ), (5α,13α)-3-hydroxy-17-aza- d -homoandrostans ( 15 ), and (5α,13α)-3-hydroxy-17-azaandrostans ( 17 ), were designed and synthesized as key precursors for the further preparation of a new family of potential GABA A receptor modulators from commercially available natural steroids (5α)-3-hydroxyandrostane-17-ones ( 7 ).