Microbial transformations of natural antitumour agents. Part 5. The structure of a novel vindoline dimer produced by Streptomyces griseus

Identification of the Major Degradation Products of Vinorelbine by Frit-FAB LC/MS and NMR

“…8 The substructure of compound 4, a reduced form of vindoline ether, was reported to be generated by microorganism biotransformation. 6 Although the reaction mechanism under the conditions of the present study is not clear, photochemical abstraction of a hydrogen atom might be responsible.…”

“…6,7 The reaction was proposed to begin with one electron oxidation at a nitrogen atom and to proceed via a reactive imminium intermediate. Given the structure of 2, its molecular weight was calculated to be 776.…”

Vinblastine and vincristine are inhibitors of monoamine oxidase B

“…The importance of the D-Phe2-Ile3 dipeptide in the cyclic hexapeptide series suggests a possible structural homology with the identical dipeptide14 or the n-(OEt)Tyr2-Ile3 dipeptide moiety4 found in many oxytocin antagonists more closely related to the structure of the hormone. Consistent with this idea is the observation that D-iOEtjTyr2 analogue 13 possesses good binding affinity. This homology, however, has not offered fully predictive value for antagonist design.…”

“…

Boc-Z6-Pro'-OR I" I* Fmoc-Ile-D---, BOP (6,12) (Cbz-or Fmoc-)-W1 2-Ile3"X4"Y5 6-Z6"Prol-OR"(a) HC1 or TFA; Boz-Z6-OH, BOP;6 (b) HC1; Fmoc-Y6-Cl or Fmoc-(Ar<-Boc)Orn-OH, BOP (6, 8); (c) piperidine or Et2NH; Fmoc-X4-Cl; (d) piperidine or Et2NH; Fmoc-Ile-Cl or Fmoc-Ile-Cl/AgCN/toluene/80 °C (3,5,13) or Fmoc-Ala-Cl ( 15); (e) piperidine or Et2NH; Fmoc-W2-OH, BOP or Fmoc-D-Phe2-Cl (2) or Cbz-D-Phe2-Cl (3) or Boc-D-(0-Et)TyrOH, BOP (13); (f) piperidine or EtjNH; NH2NH2 or H2, Pd(OH)2 (3) or HC02H (13); (g) i-C5HnONO or DPPAC (3, 4, 13); compounds 6 and 8 were obtained by treatment with HC02H and TFA, respectively, to remove the N3-Boc group on Orn5; compound 9 was obtained by hydrogenolysis (H2, Pd(OH)2) to remove the :Y6-Cbz group on Ppz5; compound 5 was obtained by hydrogenolysis (H2, Pd(OH)2) to remove the (V8-Cbz group on D-Piz4, followed by oxidation to D--4 with t-C. F. Homnick (HPLC analysis), J. P. Moreau (elemental analysis), and V. W. Finley (manuscript preparation). We also thank Dr. P. S. Anderson for encouragement and support.

…”

Voafrine A and Voafrine B, New Dimeric Indole Alkaloids from Cell Suspension Cultures of Voacanga africana Stapf

“…Sometimes cell suspension cultures might be contaminated by slowly growing microorganisms. To exclude a microbial dimerization of tabersonine before the isolation, which is well-known in the case of vindoline [14], Voacangu cells were plated on different media. After incubation at 35 "C for up to 30 days, microbial infections of the plant cells were not detected, which demonstrates that indeed the Voucunga cells synthesize voafrine A and B.…”