Total synthesis of MECA-79

Abstract

The MECA-79 antigen is a sulfated mucin type core-1 extended O-glycan which is a potential antiinflammatory agent. Herein we report a total synthesis of MECA-79 via a convergent [2 + 2] glycosylation route. The synthesis relies on efficient transformation of D-glucosamine into the orthogonally protected Tn antigen derivative and its elaboration into the TF antigen en route to MECA-79. Scheme 4 Global deprotection and completion of the synthesis of MECA-79. 58574 | RSC Adv., 2014, 4, 58573-58580 This journal is

Scalable Synthesis of Anomerically Pure Orthogonal-Protected GlcN3 and GalN3 from d-Glucosamine

“…The guidelines for substitution of glycoside nonanomeric triflates with external nucleophiles have recently been updated . A third option is anchimeric assistance leading to migration of an ester protecting group from the 3- O by substituting the 4-OTf of a glucopyranoside, causing inversion of stereochemistry; this is usually seen for pivaloyl esters but has also been observed for the acetyl group (Scheme c). However, pivaloyl is not an attractive protective group as it cannot be removed selectively and under mild conditions.…”

“One-Pot” Protection, Glycosylation, and Protection–Glycosylation Strategies of Carbohydrates

“…In the investigation of the glucosamine-derived tetra- O -TMS ether 69 , 4,6- O -benzylidenation followed by 1,3-di- O -acetylation provided the 1,3-diacetate, which was treated with ammonia gas to regioselectively remove the anomeric acetyl group to furnish reducing sugar 119 in 59% yield. This protocol could be scaled up and has been applied in the total synthesis of potential anti-inflammatory antigen MECA-79 by Kulkarni and co-workers …”

“…This protocol could be scaled up and has been applied in the total synthesis of potential anti-inflammatory antigen MECA-79 by Kulkarni and co-workers. 199 1,6-Anhydrohexopyranoses are important starting materials for preparing building blocks for the carbohydrates synthesis. 200 The conversion of hexopyranoses into 1,6-anhydrohexopyranoses forms a bicyclo[3.2.1]octane structure, which not only converts the 4 C 1 chair conformation of D-form pyranoses into 1 C 4 conformation but also reverses the axial−equatorial orientations of the hydroxyl groups exactly opposite to those of the ordinary hexopyranoses; thus, the whole reactivity pattern is altered.…”