Stereoselective Synthesis of Polyhydroxycycloheptanes and Their Phosphate Derivatives from 8‐Oxabicyclo[3.2.1]octenes. Issue 12 (4th March 2013)

• Record Type: Journal Article
• Authors: Khlevin, Dmitry A.; Sosonyuk, Sergey E.; Proskurnina, Marina V.; Zefirov, Nikolay S.
• Is Part Of: European journal of organic chemistry. Issue 12(2013)
• Page Start: 2381
• Page End: 2388
• Publication Date: 2013-03-04
• Subjects: Cyclitols -- Carbasugars -- Phosphorylation -- Dihydroxylation -- Inhibitors -- Enantioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201201426
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: The first directed synthesis of seven‐membered mono‐ and tris‐phosphates is described. The key steps involve a DIBAL‐H/DIBAL‐Cl‐mediated ring opening of 8‐oxabicyclo[3.2.1]octenes in the presence of [Ni(acac)2 ] and stereoselective syn ‐dihydroxylation with NMO and OsO4 . An enantioselective approach to ring opening has been examined with chiral phosphane. The phosphorylation of mono‐ and triols followed by deprotection gave the corresponding phosphates in high yields with structures similar to those of known inhibitors of myo ‐inositol monophosphatase (IMPase) and myo ‐inositol tris‐phosphate receptor ligands. The inhibitory activities of the monophosphates thus formed were evaluated against IMPase. Abstract : New seven‐membered cyclitols have been synthesized from 8‐oxabicyclo[3.2.1]octenes by ring‐opening followed by dihydroxylation. High enantioselectivity was observed with ( R )‐BINAP as ligand. The polyhydroxycycloheptanes thus prepared were phosphorylated to yield mono‐ and tris‐phosphates, which can be considered as homoanalogues of inositol derivatives involved in the signal transduction pathway.