Preparation of Aminoalkyl Chlorohydrin Hydrochlorides: Key Building Blocks for Hydroxyethylamine-Based HIV Protease Inhibitors
- 1 January 1996
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (11) , 3635-3645
- https://doi.org/10.1021/jo960109i
Abstract
Enantiomerically pure N,N-dibenzyl-α-amino aldehydes reacted with (chloromethyl)lithium, generated in situ from bromochloromethane and lithium metal, to give predominantly erythro aminoalkyl epoxides. Treatment of the crude epoxides with aqueous hydrochloric acid gave crystalline (2S,3S)-N,N-dibenzylamino chlorohydrin hydrochlorides in 32−56% overall yield and high isomeric purity. These compounds are versatile synthetic intermediates for the preparation of hydroxyethylamine-based HIV protease inhibitors, either directly as such, or via conversion to the corresponding N-Boc-(2S,3S)-aminoalkyl epoxides. The processes described do not make use of hazardous reagents or intermediates, do not require chromatographic purifications, and are thus amenable to the preparation of large quantities of these versatile building blocks.Keywords
This publication has 48 references indexed in Scilit:
- Stereoselective Synthesis of Erythro α-Amino EpoxidesTetrahedron Letters, 1995
- A Convenient Synthesis of 1-(S)-[1’-(S)-(t-Butyloxycarbonylamino)-2’-phenylethyl]oxirane, a Versatile Intermediate for the Preparation of Hydroxyethylamine Based HIV Protease InhibitorsSynlett, 1995
- Enantiomerically Pure Amino Alcohols and Diamino Alcohols from L-Aspartic Acid. Application to the Synthesis of Epi- and DiepislaframineThe Journal of Organic Chemistry, 1994
- A synthetic route to anti aminoalkyl epoxides by stereocontrolled reductive amination of ketoepoxidesJournal of the Chemical Society, Chemical Communications, 1994
- Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitorBiochemical and Biophysical Research Communications, 1990
- In situ formation and reactions of chloromethyl-lithium under sonochemical conditionsJournal of the Chemical Society, Chemical Communications, 1988
- Stereoselective Synthesis of β‐Amino Alcohols from Optically Active α‐Amino AcidsAngewandte Chemie International Edition in English, 1987
- Complete nucleotide sequence of the AIDS virus, HTLV-IIINature, 1985
- New methods and reagents in organic synthesis, 29, A practical method for the preparation of optically acive N-protected .ALPHA.-amino aldehydes and peptide aldehydes.CHEMICAL & PHARMACEUTICAL BULLETIN, 1982
- Sulfur trioxide in the oxidation of alcohols by dimethyl sulfoxideJournal of the American Chemical Society, 1967