Synthesis of 1-O-alkyl-2-O-methyl-glycerophospholipids with potential antitumor activity.
Some synthetic alkyl-lysophospholipid analogs have been described as a new class of immunopotentiating and antitumor agents. Among them, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine has been reported to possess the highest antitumor activity. A new method for the synthesis of this compound and of the ethanolamine- and serine-containing analog is reported. 1-Alkyl-2-methyl-rac-glycerol, prepared from 1,2-isopropylidene-glycerol, is phosphorylated and the intermediate is condensed either with N-t-BOC-protected ethanolamine or with N-t-BOC-protected serine benzhydryl ester. The choline-derivative is obtained by methylation with CH3I of the ethanolamine derivative. The same synthetic sequence has been used also for synthesizing compounds unsaturated at the fatty alkyl chain in position 1 of the glycerol moiety. Preliminary observation are reported on the selective cytolytic action of the compounds on a tumor cell line.
Alunni-Bistocchi
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G
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Italia.
Orvietani
P L
PL
Ricci
A
A
Binaglia
L
L
Orlando
M
M
Orlando
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D010742:Phospholipid Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C026659:edelfosine