63 Pd触媒による一酸化炭素挿入反応を利用した1,4-Benzodiazepine骨格の合成並びにその天然物合成への応用

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A new synthetic method of benzolactams developed by us was extended to the synthesis of 1,4-benzodiazepine derivatives(4) by insertion of carbon monoxide into the aryl halide(3), which was prepared from o-haloaniline derivatives(1) and amino acid(2). For the amino acid, glycine was chosen for the synthesis of 1,4-benzodiazepine derivatives and proline gave pyrrolo-1,4-benzodiazepine derivatives. There are many naturally occurring and biologically active substances having these skeletons. This method has led to the synthesis of diazepam, cyclopeptine(6), cyclopenin(7) and cyclopenol(8). Moreover, a total synthesis of SEN-215(15) and a formal synthesis of anthramycin(9) were also achieved by use of this method. On the other hand, one step synthesis of 1,4-benzodiazepine derivatives from o-haloaniline and amino acid was effected under 5 atm pressure of carbon monoxide in the presence of a catalytic amount of Pd(OAc)_2 and PPh_3, and K_2CO_3 as base in xylene. This method was very effective for one step total synthesis of 1-cyclopeptine(6) from o-iodoaniline and methyl N-methylphenylalanate. Similarly, compounds 48 and 49 were prepared from methyl prolinate and methyl pipecolinate at a stretch. Compound 50 was considered to be a useful intermediate for the synthesis of neothramycin(12), which was prepared from 24 and methyl prolinate.
天然有機化合物討論会の論文
1983-09-15