Enantioselective Synthesis of (2S,3R)-3-Hydroxy-3-methylproline, A Novel Amino Acid Found in Polyoxypeptins

Abstract

The enantioselective synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) was achieved by the Sharpless AD, regioselective opening of cyclic sulfate by NaN(3) and intramolecular ring-closing reaction. The reported route has the advantage of a high overall yield and good enantiomeric purity, as well as starting from readily available chemical substrates and inexpensive reagents.

Synthesis of Unusual N-Acylated Aminosugar Fragments of Mycobacterium marinum Lipooligosaccharide IV

“…To reduce the hemiaminal 56 to an N-methyl group (i.e., compound 57), we initially As was the case for 5, comparison of the NMR data for 8 with that reported for the polysaccharide was prohibited by the insolubility of 8 in D 2 O, the solvent used for NMR studies of the naturally-occurring glycan. In this context it should be noted that the synthesis of the enantiomer of 16, which could also be prepared from 3-butynol using the route described previously, 14 would enable the production of a lactam that could be used to prepare a derivative 8…”

Total Synthesis of Depsilairdin

“…Kobayashi et al were the first to synthesize the amino acid 163 starting from geraniol. 66 After this report, the groups of Hamada, [67][68][69][70][71] Yao, 72,73 Merino, 74 Davis 75 and Ye 76 also successfully reported the preparation of (2S,3R)-3-hydroxy-3-methylproline and selected syntheses are described below.…”

Methods for the Chemical Synthesis of Noncoded α‐Amino Acids found in Natural Product Peptides

“…Apart from their interesting biological activity, polyoxytoxins A and B contain the unusual CAA (2S,3R)-3-hydroxy-3-methylprolines (3-OH MePro) 20 (Scheme 5.5). Recently, enantioselective preparation of 3-OH MePro has been the focus of many research groups in response to the need for methodology to produce 3-OH MePro in large quantities for the total synthesis of the polyoxytoxins [48][49][50][51][52][53][54][55][56][57].…”

“…Yao et al prepared 3-OH MePro from the inexpensive starting material, 3-butyn-1-ol 25, utilizing a Sharpless dihydroxylation reaction as the key step [50]. The alkyne starting material was converted into a (2Z)-a,b-unsaturated ester in three steps followed by the Sharpless dihydroxylation of the trisubstituted olefin, using AD-mixa, to afford the dihydroxylated compound in 90% yield with 91% enantiomeric excess (Scheme 5.7).…”