title: Tuning the stereoelectronic properties of 1-sulfanylhex-1-enitols for the sequential stereoselective synthesis of 2-deoxy-2-iodo-β-D-allopyranosides.
abstract: The preparation of challenging 2-deoxy-2-iodo-β-D-allo precursors of 2-deoxy-β-D-ribo-hexopyranosyl units and other analogues is reported using a robust olefination-cyclization-glycosylation sequence. Here, we particularly focus on tuning the stereoelectronic properties of the alkenyl sulfides intermediates in order to improve the diastereoselectivity of the cyclization step and, hence, the efficiency of the overall transformation. Phosphine oxides with the general formula Ph2P(O)CH2SR (R = t-Bu, Cy, p-MeOPh, 2,6-di-ClPh, and 2,6-di-MePh) were easily synthesized and subsequently used in the olefination reaction with 2,3,5-tri-O-benzyl-D-ribose and -D-arabinose. The corresponding sugar-derived alkenyl sulfides were submitted to a 6-endo [I(+)]-induced cyclization, and the resulting 2-deoxy-2-iodohexopyranosyl-1-thioglycosides were used as glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodohexopyranosyl glycosides. Among the different S-groups studied, t-Bu derivative was the best performer for the synthesis of cholesteryl 2-deoxy-2-iodomannopyranosides, whereas for the synthesis of 2-deoxy-2-iodoallopyranosides none of the derivatives here studied proved superior to the phenyl analogue previously described. Glycosylation of cholesterol with different d-allo and d-manno derivatives produced 2-deoxy-2-iodoglycosides with stereoselectivities in the same order in each case, reinforcing the involvement of an oxocarbenium ion as the common intermediate of this crucial glycosylation step.
authors.affiliation: Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili , C/Marcel·lí Domingo s/n, 43007 Tarragona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kövér
authors.forename: Omar
authors.initials: O
authors.lastname: Boutureira
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Matheu
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Díaz
authors.forename: Sergio
authors.initials: S
authors.lastname: Castillón
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D003500:Cyclization; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012266:Ribose; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C000594396:(tert-butylsulfanylmethyl)diphenylphosphine oxide; D000475:Alkenes; D006027:Glycosides; D010720:Phosphines; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D013865:Thioglycosides; D012266:Ribose