Synthesis of aryl-thioglycopeptides through chemoselective Pd-mediated conjugation

Abstract

A highly chemoselective thioglycoconjugation method of iodoaryl aminoacids, small peptides and complex unprotected polypeptides is reported.

Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency

“…Under these conditions, the final compound could be then obtained in 56% yield. We recently reported an efficient method allowing the introduction of glycosyl thiols to various iodo(hetero)aryles, [40] nucleic acids [41] and peptides , [42] under simple and mild conditions using the palladium G3-Xanthphosbiphenyl precatalyst (Ref Chem Sci 2013 Buchwald et ACS Catal. 2015, 5, 1386-1396 ) .…”

“…) 13. C NMR (75 MHz, MeOD) δ 182 42,. 168.61, 163.31, 162.98, 160.42, 154.23, 141.98, 128.26, 127.97, 127.40, 126.41, 125.20, 108.58, 103.59, 101.91, 61.64, 53.74, 51.65, 43.83, 31.96, 28.28, 27.56, 27.20, 24.80, 18.04;  max 1645, 1410, 1373, 1202, 1101, 1065, 1036, 896, 819, 749, 699, 621, 561 cm -1 ; HR-ESIMS: m/z 553.2015 [M + H] + (calcd for C 29 H 33 N 2 O 7 S, 553.2008); HPLC purity, >90 % (t R = 10.54 min).…”

Tyrosine Conjugation Methods for Protein Labelling

“…The aim of this article is to review the promising chemical methods for Tyr labelling published over the last 15 years (Figure 1) and their implementation. Recently published labelling methods on non‐natural Tyr analogues (such as aryl halides), [23] or highly reactive ortho ‐quinone, are deliberately omitted [24, 25] …”

Direct, stereoselective thioglycosylation enabled by an organophotoredox radical strategy

“…Strategies involving an ionic 2e À transfer pathway have dictated the C-S bond formation development. [7][8][9][10][11][12][13] Direct replacement by a thiol with a glycosyl donor is an attractive approach in that both starting materials are readily accessible, but gives a mixture of a/b anomers in most cases (Scheme 2a). 8 To overcome these limitations, the methods of reversing the polarity at the anomeric carbon have been developed (Scheme 2b).…”

“…9a Indirect methods using preformed anomeric thiols offer versatile approaches to thioglycosides (Scheme 2c). [10][11][12][13] Nonetheless, the anomeric stereoselectivity of these processes depends on the nature of the anomeric thiols. In particular, few methods are capable of selectively constructing the challenging a-1,2-cis-thioglycosides, 8b featured in a number of natural products and bioactive molecules (Scheme 1).…”