A study of the oxepane synthesis by a 7-endo electrophile-induced cyclization reaction of alkenylsulfides. An approach towards the synthesis of septanosides

Abstract

A procedure for the stereoselective synthesis of 2-deoxy-2-iodo-septanosides from pyranoses is reported. The procedure involves two reactions: Wittig-Horner olefination to give alkenyl sulfanyl derivatives, and electrophilic iodine-induced cyclization to give phenyl 2-deoxy-2-iodo-1-thio-septanosides (20) or 2-deoxy-2-iodo-septanosides (26a,b), in this case by subsequent hydrolysis of a phenylsulfanyl group under the reaction conditions. The seven membered ring of septanosides was only formed in moderate to low yields, preferably through a 7-endo cyclization, when an isopropylidene group was present as protecting group. The use of benzyl groups as protecting moieties in the pyranose does not afford the septanoside ring. However, when the reactions conditions were forced using more basic media, the furanoside derivatives 3 were obtained.

Synthesis of 2-Iodoglycals, Glycals, and 1,1‘-Disaccharides from 2-Deoxy-2-iodopyranoses under Dehydrative Glycosylation Conditions

“…Recently, we reported the synthesis of 2-deoxy-2-iodohexopyranosyl thioglycosides 2 that are efficient glycosylating agents for the stereoselective synthesis of 2-deoxy-2-iodoglycosides and oligosaccharides 4 . The key step in the synthesis of these donors was the cyclization of alkenyl sulfanyl derivatives 1 with iodonium reagents (Scheme , path a) . The reaction time and temperature had to be carefully controlled.…”

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

“…An early isolation of septanose was achieved through cyclization of generic hexose sugars, which afforded minor amounts of septanose, along with furanose and pyranose, which formed in major amounts [ 3 ]. Synthetic approaches to septanoses have been explored in many instances, for example, (i) hemiacetal or acetal formation from a linear precursor containing aldehyde and an appropriately positioned hydroxyl group [ 4 – 8 ]; (ii) Knoevenagel-type condensation of sugar aldehyde with active methylene compounds [ 9 – 10 ]; (iii) ring-closing metathesis reactions of appropriately installed diene derivatives [ 11 – 13 ]; (iv) ring expansion of 1,2-cyclopropanated sugars [ 14 – 17 ]; (v) Baeyer–Villiger oxidation of inositol derivatives [ 18 – 19 ] and (vi) electrophile-induced cyclization [ 20 ]. We recently developed a new methodology to prepare septanosides, which involved a sequence of dihalocarbene insertion on to an oxyglycal, ring opening of the cyclopropyl moiety with a nucleophile, and oxidation and reduction reactions, so as to permit the expansion of six-membered pyranoses to seven-membered septanosides [ 21 – 23 ].…”

Synthesis of Aryl, Glycosyl, and Azido Septanosides through Ring Expansion of 1,2-Cyclopropanated Sugars

“…These ring-expanded sugars adopt flexible conformations. Few synthetic methods have been known previously to prepare septanoses and septanosides − and are studied further for their conformations. − Recent biological studies − such as protein binding studies provide evidence for the ability of the septanoside derivatives to bind proteins.…”