Synthesis of phosphoric acid diesters of 7β- hydroxycholesterol and of carbohydrates

• Published in: Tetrahedron Vol. 50; no. 22; pp. 6569 - 6578
• Main Authors: Pannecoucke, Xavier, Schmitt, Gaby, Luu, Bang
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 1994; Elsevier
• Subjects: Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Exact sciences and technology; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ANTITUMOR-ACTIVITY; DEOXYNUCLEOSIDE PHOSPHORAMIDITES; DEOXYOLIGONUCLEOTIDES; OXYSTEROL DERIVATIVES; Steroid; Aldose; Secondary alcohol; Aliphatic compound; Phosphorus Organic compounds; Allylic compound
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(01)89687-3

In order to enhance the antitumor efficacy of 7β-hydroxycholesterol by targetting its action to defined organs, the phosphoric acid esters of 3(7β-hydroxycholesteryl) and of 6(galactopyranosyl) 1 or 6(mannopyranosyl) 2 were synthesized by the phosphoramidite method (with protected C-1, 2, 3, 4 hydroxyl groups for the carbohydrates). As the protection of the sugars increased the length of the synthesis, we decided to use the hydrogen-phosphonate methodology which leads to a selective phosphorylation at the primary alcohol of carbohydrates and avoids the use of protected carbohydrates. Compound 2 was synthesized in good yield. However compound 1, probably due to steric hindrance, could not be obtained by this second method. The sodium salt of 3β(7β-hydroxycholesterol) 6(carbohydrate) monophospate ( 1 or 2) has been synthesized using both the phosphoramidite and the hydrogen phosphonate methods.