N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds.

Iwona E Głowacka,Andrzej E Wróblewski,Dorota G Piotrowska,Aleksandra Trocha

doi:10.3762/bjoc.15.168

Iwona E Głowacka, Andrzej E Wróblewski + Show 2 more

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https://doi.org/10.3762/bjoc.15.168

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Abstract

Since Garner’s aldehyde has several drawbacks, first of all is prone to racemization, alternative three-carbon chirons would be of great value in enantioselective syntheses of natural compounds and/or drugs. This review article summarizes applications of N-(1-phenylethyl)aziridine-2-carboxylates, -carbaldehydes and -methanols in syntheses of approved drugs and potential medications as well as of natural products mostly alkaloids but also sphingoids and ceramides and their 1- and 3-deoxy analogues and several hydroxy amino acids and their precursors. Designed strategies provided new procedures to several drugs and alternative approaches to natural products and proved efficiency of a 2-substituted N-(1-phenylethyl)aziridine framework as chiron bearing a chiral auxiliary.

Highlights

The synthesis of enantiomerically pure compounds belongs to the most challenging tasks in organic chemistry for several reasons, just to mention structural studies of natural products or preparation of chiral drugs
The structurally simplest chirons containing three carbon atoms and one stereogenic center can be exemplified by derivatives of ᴅ-glyceraldehyde [2] (2,3-O-isopropylidene 1a [3,4] and 2,3-O-cyclohexylidene 1b [5,6]) and (2R,5R,6R)-5,6dimethoxy-5,6-dimethyl-1,4-dioxane-2-carbaldehyde (2) [7] (Figure 1) which could be prepared from ᴅ-mannitol
Since the pyrrolidine (2S,3S,4R)-182 has three stereogenic centers of the same configuration as in (2S,3S,4S)-159 its synthesis started from the common intermediate diol 160 (Scheme 41) with the aziridine ring opening to produce the Syntheses of 1,4-dideoxy-1,4-imino-ᴅ-arabinitol ((2R,3R,4R)182) and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ((2R,3S,4S)-182) were accomplished starting from the aziridine (E)-acrylate (2S,1'R)-69b readily prepared from the aldehyde (2R,1'R)-6 (Scheme 48) [31]

Summary

Introduction

The synthesis of enantiomerically pure compounds belongs to the most challenging tasks in organic chemistry for several reasons, just to mention structural studies of natural products or preparation of chiral drugs. The synthesis of amino alcohols of general formula 11 (Scheme 3) from 2-substituted N-(1-phenylethyl)aziridines 5 and 6 can be achieved by a regioselective reductive aziridine ring opening combined with functionalization of the C2 substituent and optional alkylation or arylation of the nitrogen atom [44].

Results

Conclusion