Masafumi Arita

Design, synthesis, and structure-activity relationships of 2-substituted-2-amino-1,3-propanediols: Discovery of a novel immunosuppressant, FTY720

FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride), a novel synthetic immunosuppressant led by modification of ISP-I (myriocin, thermozymocidin) displayed potent immunosuppressive activity both in vitro and in vivo.

Simple compounds, 2-alkyl-2-amino-1,3-propanediols have potent immunosuppressive activity

Abstract ISP-I (myriocin, thermozymocidin) was structurally simplified to give 2-amino-2-alkyl-1,3-propanediols that were also potent immunosuppressants. Among the series, 2-amino-2-pentadecyl-1,3-propanediol most actively prolonged rat skin allograft survival and was more effective than ciclosporin.

Synthetic studies on biologically active natural products by a chemicoenzymatic approach: Enantioselective synthesis of C- and N-nucleosides, showdomycin, 6-azapseudouridine and cordycepin

Abstract An efficient synthesis of C- and N-nucleosides has been developed in an enantioselective and stereocontrolled manner starting from Diels-Alder adduct of furan and dimethyl acetylenedicarboxylate by chemicoenzymatic strategy. The symmetric unsaturated dimethyl esters 2 and 3 were almost quantitatively hydrolysed with pig liver esterase to yield half-esters 4 and 5 with reasonably high optical yields. Decarboxylative ozonolysis of the chiral half-esters 4 followed by chemical transformation afforded methyl L -riboside 12, but after the enantiomer conversion (4 to 13 and 5 to 28) the methyl D -riboside (17), ( + )-showdomycin (22), and ( − )-6-azapseudouridine (27), were obtained from 13, and ( − )-cordycepin (32) was obtained from 28.

Enantioselective synthesis of new analogs of neplanocin A and their biological activity

Abstract Various carbocyclic nucleosides analogs of neplanocin A (such as 5-aminoimidazole-4-carboxamide riboside, uridine, 5-iodouridine, 4-thiouridine, cytidine, thymidine, 2′-deoxyguanosine, ribofuranosylthymine, a 2,2′-anhydroderivative, 2′-deoxycytidine, 2′-deoxythiouridine, and d -arabinofuranosylcytosine analogs) were synthesized from (1 R , 2 S , 3 R )-2,3-isopropylidenedioxy-4-methoxymethyloxymethyl-4-cyclopentenylamine. The cytidine analog was found the most active in inhibiting mouse lymphoma L5178Y cells in vitro at a concentration as low as 0.8 μg/mL.