Maysine synthesis

Lee, E.A. et al.. Genetic mechanisms underlying apimaysin and maysin synthesis and corn ear-worm antibiosis in maize Zea mays L.), Genetics, 149, 1997, 1998. 

Such routes have been used for the synthesis of natural products terpenes such as egomaketone (3-(4-methyl-3-pentenoyl)furan, perillene, ar-turmerone and iso-ar-turmerone [341], ar-curcumene [152], artemisia and isoartemisia ketones [342, 343], damascone [344], macrolides such as maysine [345], and pheromones with the sex attractant of the pine saw-fly [346],... 

The potential of this sequence was applied in Meyers s total synthesis of antibiotic maytansinoids such as (-)-maysine [345]. 

The enantiotopic discrimination of hydrogens during oxidation of unactivated C—H bonds by microorganisms is synthetically extremely useful, and some examples are shown in Scheme The resultant products are valuable chiral synthons. For example (/ )-3-hydroxybutanoic acid (7) a versatile homochiral synthon, can be used in the synthesis of antibacterials. > (5)-2-Methyl-3-hydn>xypropanoic acid (8) has been widely employed as a source of chirality, for example in the synthesis of maysine, macrolide antibiotics and both (/ )- and (S)-muscone. A variety of other optically active 3-hydroxy aliphatic carboxylic acids can be prepared by analogous methods. 

Oxidation. Meyers et aV used Saigo s reagent (1) for oxidation of the primary alcohol 2 to 3 (70.5% yield). The reaction was one step in the total synthesis of maysine (4). 

For the synthesis of the 4,5-epoxy derivative, namely maysine and for that of the 3-hydroxy-4,5-epoxy derivative, maytansinol required for maytansine a number of further problems had to be surmounted. The aldehyde from step xiv (R = Me) resulting from the deketalisation of Q (R = Me) and C3 chain extension was the starting point. A new chiral centre, to avoid epimer separation, was introduced by the use of the reagent, (R)-(+)-4-tolyl phenoxycarbonylmethyl sulphoxide prepared by route (e). The synthesis of maytansinol is shown in (f). 

The key intermediate 79 was demonstrated for the synthesis of maysine as illustrated in Scheme 10. This compound 79 was reduced to the alcohol 80 and the olefin C4 5 was epoxidized with f-butylhydroperoxide and Ti(IV) catalyst (without any chiral auxiliary) to yield selectively the P-epoxide 81. Oxidation with MCPBA, on the other hand, selectively provided a-epoxide 82. These selectivities were found to be due to substrate control but not to reagent control. Sharpless condition with chiral auxiliary in this case showed substrate... 

Thiophilic addition to dithioesters followed by capture of the thioacetal anion with an electrophile provides a useful approach to the formation of carbonyl compounds such as (42) and (43), and has been elegantly employed in the total synthesis of the macrocycles ( )-maysine and ( )-4,5-deoxymaysine. Trimethyl borate has been used to convert bis(phenylthio)methyl-lithium into the keten thioacetal (45) via the boron-containing carbanion (44), as shown in Scheme 4. Bis(phenylthio)methyl-lithium and related compounds are also the key reagents in the preparation of 2-(phenylthio)-enones, 2-(phenylthio)-butadienes, a-(phenyl-... 

An efficient method for the conversion of iV>alkyl-lactams into the corresponding thiolactams, involving treatment with R3O+BF4- followed by NaSH, is reported. Twenty-four-membered macrocyclic amides containing phenylalanine and leucine units have been obtained. A total synthesis of the natural product bastadin-6, which has a 28-membered lactam ring, has been described, and total syntheses of ( )-maysine and ( >ma5dansinol are reported. ... 

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