Synthesis of 3-C-Branched Kdo Analogues via Sonogashira Coupling of 3-Iodo Kdo Glycal with Terminal Alkynes

Abstract

A highly efficient approach for the synthesis of 3- C-branched mono- and di-3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) enyne analogues is developed for the first time based on Sonogashira coupling of terminal alkynes with 3-iodo Kdo glycal obtained by the NIS/TMSOTf-promoted one-step reaction from peracetylated Kdo ethyl ester. Further transformation of 3- C-branched mono- and di-Kdo enyne analogues by asymmetric hydrogenation and saponification provided 2-deoxy-β-carboxyl Kdo analogues in a stereocontrolled mode.

Advances in Pd-catalyzed C–C bond formation in carbohydrates and their applications in the synthesis of natural products and medicinally relevant molecules

“…Inhibiting Kdo transferases (WaaA) involved in lipid A-Kdo 2 biosynthesis is, therefore, an exquisite target for antibiotics. Yang and co-workers 96 developed a cross-coupling methodology for the functionalization of the 3-iodo-Kdo-glycals 182 with terminal alkenes 183 and acetylenes 185 under Pd catalysis for the synthesis of 3- C -branched 3-deoxy- d -mannooct-2-ulosonic acid (Kdo) analogues ( Scheme 47 , 184, 186). The substrate scope of the reaction was further enhanced with variety of terminal akenes and acetylenes.…”

Base-Mediated Transformation of Glycals to Their Corresponding Vinyl Iodides and Their Application in the Synthesis of C-3 Enofuranose and Bicyclic 3,4-Pyran-Fused Furanose

“…Further, glycals having double bonds functionalized with halogen (vinyl iodides) are valuable synthons in the total synthesis of natural products and biologically active scaffolds due to the ease of metal-catalyzed C–C bond formation using Heck, Suzuki, Sonogashira, and some carbonylation reactions. A few examples of the importance of C-2-vinyl iodides in the synthesis of various bioactive compounds based on certain types of scaffolds like disaccharide mimetics, kdo sugar, thioglycosides, C-2 branched glycoconjugates, amides, oxadecalines derivatives like 1-oxadecalines and core of phomactin A, some anthracyclines derivatives, indulines, and some natural products like bradhyrhizose are depicted in Figure . Due to the vast importance of 2-iodoglycals, it is desirable to access them in large quantities directly from glycals.…”

2-Iodo-1-C-acceptor-substituted glycals: synthesis and transformation into 1,2-C,C-disubstituted glycals via Suzuki–Miyaura coupling reaction

“…The synthesis of 2-halo-1- C -substituted glycals and their application in the synthesis of 2- C -branched carbohydrates are scarcely studied in the literature. Very few examples for the transformations of 3-iodoglycal of Kdo (3-deoxy- d - manno -oct-2-ulosonic acid) in a Heck-type coupling with methyl acrylate, in Sonogashira couplings with some mono- and bivalent terminal alkynes, 22 and in copper mediated perfluoroalkylation were described. 20,21…”

“…20,21 The synthesis of 2-halo-1-C-substituted glycals and their application in the synthesis of 2-C-branched carbohydrates are scarcely studied in the literature. Very few examples for the transformations of 3-iodoglycal of Kdo (3-deoxy-D-mannooct-2-ulosonic acid) in a Heck-type coupling with methyl acrylate, in Sonogashira couplings with some mono-and bivalent terminal alkynes, 22 and in copper mediated perfluoroalkylation were described. 20,21 As a continuation of our systematic study of the reactivity of 1-C-substituted glycals [23][24][25] having electron withdrawing groups (CN, CO 2 CH 3 , CONH 2 ) on the C-1 carbon, the goal of our present work was to elaborate the synthesis of 2-iodo-1-Csubstituted glycals and to study their Suzuki-Miyaura coupling reactions with boronic acids.…”