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A concise, flexible, and high-yielding synthesis of the macrocyclic compound 4 is outlined which served as a key intermediate in a previous total synthesis of the antitumor active alkaloid roseophilin 1. The key steps of this approach consist of a Pd(0)-catalyzed reaction of vinyloxirane 6 with sulfone 7 and in a subsequent ring closing metathesis (RCM) reaction for the formation of the 13-membered ring catalyzed by the ruthenium carbene Cl₂(PCy₃)₂Ru=CHCH=CPh₂ introduced by Grubbs. Moreover, nitrile ylide cycloaddition reactions are used for the preparation of roseophilin side chain mimics. Finally, the synthesis of various chromophore analogues of 1 is reported, including deschloro-desmethoxyroseophilin 12 which is the most elaborate derivative of this complex target reported so far

Table. Selected 1H and 13C NMR data of compound 12. All assignments are unambiguous and were made by using COSY and 13 C, 1 H-chemical shift correlated NMR spectra. Arbitrary numbering as shown. The multiplicity of the 13 C signals refers to the geminal protons (DEPT). Atom H NMR (8)13 NMR (8) Schematic representation of the longe range couplings observed in the nJ(H,C) correlated spectra of compound 12 which define the site of acylation of the pyrrole ring and the location of the isopropyl side chain within the cyclopentanone ring (arbitrary numbering). 10NK N 13 14 \ One might expect that strain and/or antiaromaticity of the product formed could prevent the desired elimination of the sulfone group of substrate 11 in the 5-membered ring; however, elimination in the ansa chain might occur which would lead to product 13 after the 1,4-addition of the zincate. The attached spectra, however, rigorously exclude such a pathway: (i) the observed coupling pattern (doublett) of the proton at the branching point does not match the one expected for 13 (ddd or dAB). n (ii) the observed crosspeaks of H-4 (numbering as above) in the J(C,H) correlated spectrain particular those with two quarternary pyrrolic C-atoms -give an unambiguous proof of the site of attachment.Similar arguments can be forwarded to establish the site of acylation of the pyrrole ring (10 -+ 11 -+ 12). In the product formed, crosspeaks are observed between the N-CH 2 Ph (H-11) and two quarternary oa-C-atoms of the trisubstituted pyrrole ring (C-7, C-10), while a crosspeak with its =CH atom (C-9) is missing. This excludes that acylation had occurred at C-4 of the pyrrole and hence definitely rules out the formation of the isomeric product 14. mmol) in acetone (10 ml) was stirred at 50oC for 16 h. After cooling to room temperature, the precipitated NaC1 was filtered off under argon and washed with acetone (10 ml).Tetrahydrothiophene (