The fit total synthesk of the. tranorgic myamiin fumitranorgin C (la) m@iying a-mehxy-N-hydroxyqptophm (Sa) is pmmtat. Our qroach fatura formation of the nimnc (6a). steramlahe cyclowldition to yield 7a, ring openiq and couphg with an Lpmline daivative to form 14. Bwe-catalywd cpimairh gave 16. which wan converted into h titls aqmmd by dqmJtc&m of lhe amine function& dioxopipauh fomarkm alKl dr!hydrukm.
Recently, we reported the first stereoselective approach to tetrahydro-gcarbolines (c.f. 7) having a masked C(1) 2-hydroxy-2-methylpropyl side chain moiety? Subsequent to the development of this efficient, N-hydroxytryptophan mediated synthesis of these tetrahydro-g-carbolines, one of our goals has been the synthesis of the skeleton of fumitremorgins.2 Through the synthesis of the fumitremorgin C analog 2b, we became evidence -though inconclusive-that this compound is not the skeleton of fumitremorgin C (la) but a C(14a) epimer. It should be born in mind that at that time the stereochemistry at C(14a) of the natural product was unknown.4 :o, Fumia=winC 2a,b (C(14a)cpimcr) 3%b (C(Wpii) 4a,b (C(8) and C(14a)cpimer) a: R=OMe b: R=H Unfortunately, our approach to 2b employing the cycloadduct 7b invariably led to compounds having a truns-relationship between the tetrahydro~arbolines C(1) and C(3) substituents (Scheme I). So the problem we faced was a selective epimerisation at the carbon atom C(3) of 7 or one of its successors. The second challenge to address was the introduction of the methoxy substituent at the 6position of the indole nucleus.
Reported here are solutions to both of these problems. The result is an efficient synthesis of the