Practical enantiospecific syntheses of lysobisphosphatidic acid and its analogues.
We describe a versatile, efficient, and practical method for the preparation of enantiomerically pure lysobisphosphatidic acid (LBPA), bisether analogues, and phosphorothioate analogues of LBPA from solketal. Phosphorylation of a protected sn-2-O-oleoyl glycerol with 2-cyanoethyl bis(N,N-diisopropylamino)phosphite, followed by oxidation and deprotection, generated the enantiomers of 2,2'-LBPA. The corresponding phosphorothioate analogues were obtained by oxidation with sulfur. The (R,R) and (S,S) enantiomers of both LBPA and phosphorothioate LBPA were synthesized from (S)- and (R)-solketal, respectively. The ether analogue of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer were synthesized from the same enantiomer (S)-solketal by simply changing the sequence of deprotection steps.
Jiang
Guowei
G
Department of Medicinal Chemistry, University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108-1257, USA.
Xu
Yong
Y
Prestwich
Glenn D
GD
D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D050178:Monoglycerides / Q000138:chemical synthesis* / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D013237:Stereoisomerism
D008246:Lysophospholipids; D050178:Monoglycerides; D010710:Phosphates; C012786:bis(monoacylglyceryl)phosphate; C083120:phosphorodithioic acid