The experiments described in reaction schemes 1–12 indicate that sulfide contraction via alkylative coupling (see scheme p. 729) is a potentially general method for the synthesis of secondary vinylogous amides and enolizable β-dicarbonyl compounds.

Sulfidkontraktion via alkylative Kupplung: Eine methode zur darstellung von β‐dicarbonylderivaten. Über synthetische methoden, 1. Mitteilung

Synthesen von Gallenfarbstoffen, IV1) Totalsynthese des racemischen Phycocyanobilins (Phycobiliverdins) sowie eines “Homophycobiliverdins”2)

The hydrochlorides of both enantiomers of the antibiotic anisomycin were prepared starting with the ‘diacetone-fructose’-substituted allene 1 and the N-Boc-protected imine precursor 2a. Addition of an excess of lithiated 1 to 2a provided a 2 : 1 mixture 3a of diastereoisomers, which were cyclized to 4a under base promotion (Scheme 2). The two diastereoisomers of 4a were separated and converted into enantiomerically pure pyrrolidin-3-ones (2R)-5a and (2S)-5a. A similar sequence yielded the N-Tos-protected compounds (2R)-5b and (2S)-5b. Compounds 5a were converted into silyl enol ethers 6 and by subsequent regio- and stereoselective hydroboration into pyrrolidine derivatives 7 (Scheme 3). Straightforward functional-group transformations led to the hydrochlorides 9 of anisomycin (Scheme 3). The (2R) series provided the hydrochloride (2R)-9 of the natural occurring enantiomer, whereas the (2S) series furnished the antipode (2S)-9. The overall sequence to the natural product involved ten steps with eight purified intermediates and afforded an overall yield of 8%. Our stereochemically divergent approach to this type of hydroxylated pyrrolidines is highly flexible and should easily allow preparation of many analogues.

Syntheses of Enantiomerically Pure 2-Substituted Pyrrolidin-3-ones via Lithiated Alkoxyallenes - An Auxiliary-Based Synthesis of both Enantiomers of the Antibiotic Anisomycin

The antibiotic anisomycin was first isolated by Sobin and Tanner (1954) from culture filtrates of two different species of Streptomyces, subsequently identified as S. griseolus and S. roseochromogenes (Tanner et al, 1955), and more recently the drug has also been isolated from Streptomyces sp. No. 638 
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Fig. 1A-C.
Chemical structure of anisomycin and some structurally related compounds

by Ishida et al. (1974). Crystalline anisomycin is soluble in water, and aqueous solutions appear to be more stable at slightly acidic pH (pH 4 to 6) than at alkaline pH (Tanner et al., 1955; Barbacid and Vazquez, 1973). Both the chemical structure and the stereochemical configuration of the drug were established by Beereboom et al. (1965) and Butler (1968) (Fig. 1), and its complete chemical synthesis has also been achieved (Oida and Ohki, 1969; Felner and Schenker, 1970).

Anisomycin and Related Antibiotics

Phytotoxic compounds produced by microorganisms are reviewed. Their utilisation as leads to new herbicides is explored in three chemical classes : 2-aminoalk-3-enoic acids, ether derivatives of 3-hydroxycyclobut-3-ene-1,2-diones, and 2-(acylaminooxy)acetic acid derivatives. It is concluded that some bacteria and fungi yield compounds possessing sufficient herbicidal activity to be valuable as herbicides as such, or as leads for chemical optimisation.

K. Schenker

Papers

Totalsynth. des antibioticums anisomycin