An efficient preparation of isosteric phosphonate analogues of sphingolipids by opening of oxirane and cyclic sulfamidate intermediates with alpha-lithiated alkylphosphonic esters.
D-erythro-(2S,3R,4E)-Sphingosine-1-phosphonate (1), the isosteric phosphonate analogue of naturally occurring sphingosine 1-phosphate (1a), and D-ribo-phytosphingosine 1-phosphonate (2), the isosteric phosphonate analogue of D-ribo-phytosphingosine-1-phosphate (2a), were synthesized starting with methyl 2,3-O-isopropylidene-d-glycerate (4) and D-ribo-phytosphingosine (3), respectively. Oxirane 12 was formed in eight steps from 4, and cyclic sulfamidate 22 was formed in five steps from 3. The phosphonate group was introduced via regioselective ring-opening reactions of oxirane 12 and cyclic sulfamidate 22 with lithium dialkyl methylphosphonate, affording 13 and 23, respectively. The synthesis of 1 was completed by S(N)2 displacement of chloromesylate intermediate 14b with azide ion, followed by conversion of the resulting azido group to a NHBoc group and deprotection. The synthesis of 2 was completed by cleavage of the acetal, N-benzyl, and alkyl phosphonate ester groups.
Sun
Chaode
C
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, New York 11367-1597, USA.
Bittman
Robert
R
D002384:Catalysis; D004952:Esters / Q000737:chemistry; D005027:Ethylene Oxide / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis*; D013107:Sphingolipids / Q000138:chemical synthesis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013451:Sulfonic Acids / Q000737:chemistry
D004952:Esters; D008246:Lysophospholipids; D063065:Organophosphonates; D013107:Sphingolipids; D013451:Sulfonic Acids; C060506:sphingosine 1-phosphate; D008094:Lithium; D005027:Ethylene Oxide; D013110:Sphingosine