Sequential Site-Selective Functionalization: A Strategy for Total Synthesis of Natural Glycosides

Abstract

AbstractTotal synthesis of several ellagitannins, strictinin (1), pterocarinin C (2), cercidinin A (3), and tellimagrandin II (19), is described. The key issues for the synthetic strategy rely on the catalyst-controlled site-selective acylation and stereoselective glycosylation with unprotected glucose. Total synthesis of punicafolin (5) with a glucose core in 1C4 (chair) conformation and macaranganin (30) with a glucose core in 5S1 (skew boat) conformation was also accomplished based on a similar unconventional retrosynthetic route. For success in the synthesis of 5 and 30, the flipping behavior of the pyranose ring from the stable 4C1 conformer to the unstable axial-rich 1C4 conformer is the key. Because no protective groups for glucose were employed throughout the synthesis of these natural glycosides, the total synthesis was achieved in extremely short overall steps.