Apoptolidin A: Total Synthesis and Partially Glycosylated Analogues

Abstract

The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11-C12 (cross-coupling) and C19O-C1 (macrocyclization). The cis-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue. Auxiliary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross-coupling of the glycosylated northern half with the glycosylated southern half was achieved with CuI-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.

Nucleophilic Substitution Reactions of 2‐Phenylthio‐Substituted Carbohydrate Acetals and Related Systems: Episulfonium Ions vs. Oxocarbenium Ions as Reactive Intermediates

“…[1,2] Carbohydrate-derived acetals substituted with PhS groups undergo highly diastereoselective reactions, and substrates of this type have been applied in natural product synthesis, [3] as illustrated in Scheme 1. [4] Similar observations have been made in glycosylation reactions of furanose derivatives (Scheme 2). [5] Other substituents, such as PhSe groups [6,7] and halogens (particularly I [8][9][10][11] ), have also been employed.…”

Use of sultines in the asymmetric synthesis of polypropionate antibiotics

“…Syntheses of apoptolidinone A, the aglycone of 1, were reported by the groups of Sulikowsky [143], Crimmins [144], Nicolaou [138][139][140], and Koert [141,142]. In addition, several studies on the synthesis of fragments of apoptolidinones have been reported [137,[145][146][147][148][149][150][151][152][153][154][155].…”

“…Successful total synthesis of 1 has been achieved by the groups of Nicolaou [138][139][140] and Koert [141,142]. Syntheses of apoptolidinone A, the aglycone of 1, were reported by the groups of Sulikowsky [143], Crimmins [144], Nicolaou [138][139][140], and Koert [141,142].…”

α-C-Glycosides via syn Opening of 1,2-Anhydro Sugars with Organozinc Compounds in Toluene/n-Dibutyl Ether

“…26 2,6-Anhydro-5-deoxy-1,3-O-(di-tert-butylsilanylidene)-D-arabino-hex-5-enitol (503 mg, 1.76 mmol) was then dissolved in acetone (4L/mol) under inert atmosphere (N 2 ) and the mixture was cooled down Zinc bromide lithium bromide solution in n-dibutyl ether. Inside a glovebox, a 50 mL Schlenk tube with magnetic stirrer was charged with solid zinc bromide (7.11 g, 31.6mmol), lithium bromide (2.74 g, 31.6mmol) and n-dibutyl ether (30 mL).…”