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Synthesis of Streptolidine Lactam, a Guanidine-contain ing Amino-acid Lactam Moiety of Streptothricin Antibiotic Group

1977; Oxford University Press; Volume: 50; Issue: 9 Linguagem: Inglês

10.1246/bcsj.50.2375

1348-0634

Mitsuhiro Kinoshita, Yoshiharu Suzuki,

Plant-based Medicinal Research

Streptolidine lactam (3) present in streptothricin antibiotics was stereospecifically synthesized. 3,4-Anhydro-1,2 : 5,6-di-O-isopropylidene-D-iditol (4) was converted into the 3,4-bis(benzyloxycarbonylamino)-3,4-dideoxy-D-mannitol derivative 7 via the 3,4-diazido-3,4-dideoxy-D-mannitol derivative 6. De-O-protection of 7 followed by two-stage oxidation with periodate-bromine afforded 2,3-bis(benzyloxycarbonylamino)-2,3-dideoxy-D-arabono-1,4-lactone (8), which was transformed into the azide lactone 9. Selective hydrogenolysis of 9 with Raney Ni gave the N-protected amino sugar lactam 10. O-Tetrahydropyranylation of 10 followed by hydrogenolysis afforded the O-protected amino sugar lactam 12. Treatment of 12 with cyanogen bromide in water gave the O-tetrahydropyranylated streptolidine lactam 13, which on mild acid hydrolysis afforded 3 (hydrochloride). The amino sugar lactam 14 obtained by hydrogenolysis of 9 with palladium black was also treated with cyanogen bromide to yield 3 (hydrobromide). Acid hydrolysis of 3 gave streptolidine (2) (dihydrochloride) identical with that derived from the antibiotics.