Application of DAST mediated reactions in transformations of α-hydroxyphosphonates derived from O-isopropylidene-protected carbohydrate derivatives

GRAPHICAL ABSTRACT

ABSTRACT

Various α-hydroxyphosphonates derived from O-isopropylidene glyceraldehyde, hexofuranose and pentofuranose have been prepared to test nucleophilic fluorination reactions. The substrates have been conveniently prepared in Pudovik reactions and the stereoselectivity, as well as the configuration of the obtained carbohydrates have been described. Reactions have been accomplished using DAST as the fluorinating reagent. Treatment of protected glycerol phosphonate with DAST gave unusual conversions leading to fosfomycin analogue possessing an oxirane ring. Subsequent reaction with diethylaminesulfur trifluoride (DAST) yielded β-ketophosphonate. By contrast, stereoselective deoxyfluorination of hydroxyphosphonates derived from an O-isopropylidene pentofuranose gave the major fluoride possessing D-glu configuration while the reaction with di-O-isopropylidenehexofuranose derivative, has not been successful presumably due to stereochemical properties of the substrate.

KEYWORDS:

• α-Hydroxyphosphonate
• carbohydrate
• fluorinated phosphonate
• Pudovik reaction
• rearrangement
• DAST

Funding

The research was supported by Wroclaw Research Centre EIT+ under the project ″Biotechnologies and advanced medical technologies″–BioMed (POIG.01.01.02-02-003/08) financed from the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2).