Hans-Herloff Inhoffen zuin 65. Geburtstag gewidmet (13. I. 71) Ubcr synthetische Mcthoden, 1. Mitteilung Summary. The experiments described in reaction schemes 1-12 indicate that sulfide contractlow via alkylative coupling (see scheme p. 729) is a potentially general method for the synthesis of secondary vinylogous amides and enolizablc B-dicarbonyl compounds. Projekt sind ahnliche Modellversuche unabhangig auch von R. B. Woodward und Mitarb., Harvard University, durchgefuhrt worden (Privatmitteilung Prof. R. B. Woodward).Die Erfahrung aus den von uns bisher angestellten Versuchen bezieht sich ausschliesslich auf Thiolactame. Uber die Version der oxydatiuen Kupplung bei der Darstellung von vinylogen Amidinen, 2) 3)vgl.[l].

A total synthesis of cyclothialidine (l), a new DNA gyrase inhibitor isolated from Streptomycesfilipinensis, is described. The synthetic concept was tested by preparing the lactone 13 (Scheme 2) which contains the characteristic bicyclic core entity of 1. Key features of the synthesis of 1 are: preparation of 3,5-dihydroxy-2,6-dimethylbenzoic acid (23) from 3,5-dihydroxybenzoic acid (19) by two consecutive Mannich aminomethylation/hydrogenation sequences; benzylic N-bromosuccinimide bromination of an ester derivative 25 thereof and its subsequent coupling with Boc-Ser-Cys-OMe (11); cyclization of the o-hydroxy acid 29 to the 12-membered lactone 30 using preferably Mitsunobu conditions; completion of the peptidic side chains of 1 using Boc strategy (Scheme 4 ) . Optically pure cis-N-(ter~-butoxycarbonyl)-3-hydroxy-~-proline ((-)-14) was obtained by resolution of the racemate via an efficient reaction sequence containing a lipase-catalyzed enantiospecific acetate hydrolysis (Scheme 3 ) . The structure of natural 1 was confirmed by comparison with the synthetic material. The synthetic route described provides also easy access to analogues of 1, e.g., via the intermediate 30.

the N-aryl rotation takes place at a favorable rate for NMR line-broadening measurement~[~J. However, we also introduced the achiral(4) into the investigation. In unassociated ( 4 ) it is not possible to follow the rotation by NMR spectroscopy, because the shifts of the methylene protons H i and H2 must be identical, this also being true for both methyl groups. However, ( 4 / should form an "enantiomeric association complex" with an optically active auxiliary compound, with the result that H i and

Step of the Corrin Synthesis via A ! D Ring Closure D: The Photochemical A/D-Secocorrin ! Corrin Cycloisomerization: Exploratory Studies on its Mechanism.Chapter A describes the background of the two topics discussed in Chapts. B and C within the general context of the project Corrin Syntheses.Chapter B deals with the development and application of C,C-bond formation by sulfide contraction as a general method for constructing the chromophore system in corrin ligands. The method had been developed in the context of the task of joining precursors of ring B and ring C to the B/C component in the collaborative Harvard/ ETH project of the synthesis of vitamin B 12 . Conceptually, the methods central process corresponds to an intramolecularization of an otherwise intermolecular C,C-bond formation by a (thio)imido-ester/enamine (enamide) condensation. The procedure starts by a preliminary intermolecular oxidative coupling of the S-atom of a thiolactam group with the electrophilic C-center of an enamine or enamide group to give an imidoyl-vinyl-sulfide intermediate, which, in a follow-up step, is intramolecularly contracted to a vinylogous amidine system with concomitant transfer of the S-atom to an external thiophile (cf. Fig. 3). The method has been successfully applied to the construction of A/D-secocorrin model substrates in three model series by three different strategies of connecting the four peripheral rings A, B, C and D. These strategies differ in the sequence by which these four rings are joined together (cf. Figs. 5 and 6, 10 and 11, and 13). A/D-Secocorrin complexes obtained by a B þ C ! BC þ A ! ABC þ D ! ABCD strategy served as main model substrates for the exploration of the photochemical A/D-secocorrin ! corrin cycloisomerization, whereas an A/Dsecocorrin chloro-Zn II complex constructed by a BC þ D ! BCD þ A ! ABCD strategy was the target of a model study pursued as a pacemaker synthesis for the construction of the chromophore system in the photochemical variant of the vitamin B 12 synthesis.In Chapt. C, the targeted discovery and some of the applications of the photochemical A/D-secocorrin ! corrin cycloisomerization are described. The concept of this novel process emerged for a corrin synthesis in which all four rings are derived from one single starting material, reflecting the hidden structural symmetry of the vitamin B 12 molecule. The reaction was studied in three A/D-secocorrin model systems (cf. Chapt. A), the A/D-secocorrin model in the 15-cyano-2,2,7,7,12.12-hexamethyl-1methylidene series being the one that served as the main substrate in the exploration of the reaction. The A ! D ring closure proceeded smoothly under the influence of visible light and under strict exclusion of O 2 in yields of over 90% in A/D-secocorrin complexes of the filled-shell metal ions Zn II , Cd II , Mg II , Li I , and (tentatively) also Ca II and Na I , but not for complexes of the first-row transition metals such as Ni II , Cu II , and (tentatively) Co III , Mn II , and Fe II . The reaction also occurs -more slowly...

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