62 天然物をリード化合物とする生理活性物質へのアプローチ : β-ラクタム化合物の合成

概要

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Nature provides with biologically important and structurally unique and diversified compounds. For instance, there are some biologically interesting compounds containing a partial structure derived from unsaturated α-amino acids. Thus, cyanoformates were used as synthon for the synthesis of kasugamysin (1) and virazole (2). The object of the present research is to find a new approach to the synthesis of β-lactam antibiotics (3-7), especially new target molecules such as 11, 12a, and 12b based on nocardicin A (5). The following results were obtained, providing some key intermediates of β-lactam compounds for the purpose. 1. Diethyl oxalate (13) was converted to ethylthioiminoester (16) through 14 and 15. The α,β-imino double bond (16) was moved to β,γ-imino double bond (17) with LDA and β-lactam compounds (18) were obtained as designed. 2. Rather simple synthesis of α-ethylthio β,γ-imino derivative (25) was effected from ethyl ethylthioacetate (22) in three steps, providing key intermediates of our synthesis of β-lactam compounds. 3. Unstaturated α-amino acids (10) obtained from cyanoformate and active methylene compounds were found inappropriate for further modification.
1979-09-20