2,3-Aziridino-2,3-dideoxy-d-ribono-γ-lactone 5-Phosphonate:  Stereocontrolled Synthesis from d-Lyxose and Unusual Aziridine Ring Opening

Abstract

The synthesis of (1R,4S,5S)-N-(benzyloxycarbonyl)-4-[(diethoxyphosphinyl)methyl]-3-oxa-6-azabicyclo[3.1.0]hexan-2-one (23), a new member of the 2,3-aziridino gamma-lactone family of compounds, was achieved in 15 steps from D-lyxose. Like all aziridino gamma-lactones known so far, 23 reacted with a soft nucleophile (ethanethiol) to give exclusively the product of aziridine ring opening at C-2 (24). On the other hand, hard nucleophiles (alcohols) did not react directly with the aziridine ring of 23 but appeared to promote intramolecular attack of the aziridine ring at C-3 by the C-5 phosphonate group, resulting, after hydrolytic workup, in formation of the 2-amino-3-hydroxy-D-ribono-1,4-lactone derivatives 25 and 26, instead of the expected 2-amino-3-alkoxy-D-xylono-1,4-lactone derivatives.

Aziridine Carboxylates, Carboxamides and Lactones: New Methods for Their Preparation and Their Transformation into α- and β-Amino Acid Derivatives

“…Key steps include the transformation of a 2-O-tosyl-3-azido furanoside (e.g., 5) into an aziridine (e.g., 6) via a modified Staudinger reaction and conversion of the trialkylsilylfuranoside 7 into the desired aziridine-γ-lactone by sequential treatment with fluoride anion and TPAP [1][2][3][4].…”

Excitatory amino acids

“…A recent report details an investigation into the synthesis of more highly functionalised analogues of d-AP5 in order to improve BBB penetration. 79 The key aziridine intermediate 89, prepared in a multi-step sequence from d-lyxose, can be opened by alcohols to give the g-lactone 90 in a reaction whose regioselectivity and stereoselectivity can be understood in terms of participation of the adjacent phosphonate group. This approach would obviously provide access to hydroxylated AP5 derivatives, although the required manipulation to achieve this was not examined.…”

KOH‐Oriented Ring Openings of N‐Tosylaziridines with Carboxylic Acids in DMSO

“…Aziridines are widely recognized as significant and versatile building blocks for the synthesis of various biologically active compounds . Their activity has led to wide research and use in the ring‐opening reactions with a range of nucleophiles .…”