Masayuki Narisada

Synthetic studies on β-lactam antibiotics. Part 16. synthesis of 1-carba-2-penem-3-carboxylic acid esters from penicillins utilizing a carbon-carbon coupling reaction

Abstract Allylazetidinones 9 , 10 , prepared by coupling of allylcoppers 8 with chloroazetidinones 6 , 7 , were converted into carbapenem esters 16 , 28 – 31 using an Emmons-Horner reaction to introduce the 6-side chain and an intramolecular Wittig reaction to form the carbapenem ring system.

Synthesis of polyhedral borane derivatives having a carboxy group

Abstract Polyhedral borane derivatives having a carboxy group were synthesized by the reaction of Na210B12H11SH with Br(CH2)nCOOR in KOH and DMSO. 10B-Containing polylysine and γ-globulin are also described.

Activity of synthetic gibberellin A15 and (±)-gibberellin A15isolactone

The activities of (±)-gibberellin A15 ((±)-GA15) and (±)-gibberellin A15-isolactone ((±)-iso-GA15) which were obtained by stereocontrolled total synthesis and gibberellin A15 (E-GA15) synthesized by interconversion of enmein were assayed by the rice seedling test. As expected, (±)-GA15 showed half the activity of natural gibberellin A15 (GA15). E-GA15 which has a natural configuration showed the same activity as natural gibberellin A15 while (±)-iso-GA15 was almost inactive. These samples were also submitted to the cucumber hypocotyl assay. Contrary to what has already been reported, they were almost inactive.

1-Oxacephem Antibiotics

1-Oxacephem antibiotics, in which the 1-sulfur atom in cephalosporins is replaced by oxygen, show marked enhancement in their antibacterial activity. This finding led to intensive efforts toward establishing a stereocontrolled and industrially feasible method for their production. One method along a synthetic route involving epi-oxazoline (46), allylic alcohol (47), its cyclized 3-methylene-1- oxacepham (48) and 7α-methoxy-7β-amino-1-oxacephem (41) was found to be the most efficient for producing 1-oxacephamycin-type antibiotics, such as latamoxef (11a), flomoxef (11b), and 2355-S (11c).

A partial synthesis of aldosterone

Aldosterone was partially synthesised starting from adrenosterone by a multi-step reaction sequence. Hydrocyanation was applied successfully to a D-homo-Δ12-11-keto-steroid to furnish a 13β-cyano-11-ketone in highly stereoselective manner and in excellent yield. The 18 → 11β-lactonic function was readily derived from this cyano-ketone by a three-step synthesis, and the resulting olefinic lactone was transformed into the lactonic ketol acetate, the final product of the present synthesis, by D-ring contraction and by subsequent lengthening of the C-17 side-chain.

The significant directing effect of the cyano-group in the reduction of 5-cyano-3-oxo-steroids with complex metal hydrides

The stereochemistry of reduction of 5α- and 5β-cyano-17β-hydroxyandrostan-3-one [(la) and (Va)] and of 5α- and 5β-cyano-17β-hydroxyoestran-3-one [(lb) and (Vb)] with lithium tri-t-butoxyaluminium hydride and sodium borohydride has been investigated. Several earlier stereochemical assignments for the resulting 5-cyano-3α- and 3β-alcohols proved incorrect. In almost every case, formation of the axial alcohol is predominant, this predominance being greater with lithium tri-t-butoxyaluminium hydride in tetrahydrofuran than with sodium borohydride in ethanol. This significant directing effect of the 5-cyano-group is conspicuous and can be accounted for in terms of both steric and polar factors.