Methods for the synthesis of plasmalogens and plasmalogen derivatives, and therapeutic uses thereof

摘要

A method for preparing plasmalogens and derivatives thereof represented by Formula B, wherein R1 and R2 are similar or different, derived from fatty acids; R3 is selected from hydrogen and small alkyl groups. The synthetic route involves production of novel cyclic plasmalogen precursors of Formula A and their conversion to plasmalogens and plasmalogen derivatives of Formula B. Also disclosed is the therapeutic use of plasmalogens and derivatives thereof as produced by the synthetic route of the present invention.;

主权项

1. A process of preparing a compound represented by wherein R1 and R2 are the same or different saturated, unsaturated, or polyunsaturated C1-C28 hydrocarbon chains, and optionally derived from fatty acids; and R3 is hydrogen or a C1-C3 alkyl group, the process comprising:
a) coupling a solketel represented by Formula 1: with an allyl halide to obtain a compound represented by Formula 2: b) deprotecting the ketal present in the compound represented by Formula 2 to obtain a compound represented by Formula 3: c) protecting the diol present in the compound represented by Formula 3 to obtain a compound represented by Formula (iv): d) reacting a compound as represented by the formula X—R1 with the compound represented by Formula (iv) to obtain a compound represented by Formula (v) wherein R1 is as defined above and X is a halogen,e) deprotecting the ether groups present in the compound represented by Formula (v) to obtain a compound represented by Formula 6: f) protecting the primary alcohol present in the compound represented by Formula 6 to yield a compound represented by Formula (vii): g) esterifying a fatty acid as represented by R2—COOH to the compound represented by Formula (vii) to obtain a compound represented by Formula (viii): wherein R2 is as defined above,h) deprotecting the ether present in the compound represented by Formula (viii) to obtain a compound represented by Formula 9and
reacting POCl3 with the compound represented by Formula 9, ethanolamine, and triethanolamine (TEA) to yield the compound represented by Formula A.