NF-kB阻害剤デヒドロキシメチルエポキシキノマイシン(DHMEQ)の鍵中間体および新規類縁体の合成

The synthesis of the key intermedicate of dehydroxymethylepoxyquinomicin (DHMEQ),a potent and specific NF-kB inhibitor,was achieved. The method involved the following crucial steps:i) direct construction of quinone functionality by degradative oxidation using hypervalent iodine (III) reagents such as (diacetoxyiodo) benzene (PIDA) and [bis(trifluoroacetoxy)iodo]beneze (PIFA);ii) regioselective epoxidation of quinone having a carbamoyl group; and iii) regio- and stereoselective reduction of an epoxyquinone moiety. In addition,a novel DHMEQ analog was synthesized by applying this approach

窒素原子上に電子吸引性基を有する2-ピリドン誘導体の合成

1-Protected 2(1H)-pyridones are highly useful dienophiles because Diels-Alder reaction of 1-sulfonyl-2(1H)-pyridones gave the synthetic intermediate such as quinoline and isoquinoline derivatives. Acylation of 2(1H)-pyridone bearing a methoxycarbonyl group at the 5 or 6-position with benzoyl chloride having a some functional group (such as bromo, methoxy, nitro) gave 1-benzoylated 2(1H)-pyridone derivatives. Further, the sulfonylation of 3-cyano- and 3-methoxycarbonyl-1(2H)-isoquinolones afforded 2-sulfonylisoquinolone derivative

ヒストン脱アセチル化酵素阻害物質スピルコスタチンAの合成研究

Spiruchostatin A (1), isolated from a culture broth of Pseudomonas sp., has been shown to be a potent histone deacetylase (HDAC) inhibitor. HDAC inhibitors can suppress the growth of human tumor xenografts, this natural product, therefore, is expected to be a promising candidate for novel molecular-targeted anticancer agents. We envisioned that 1 would be synthesized through twofold macrolactam/macrolactone cyclization of the fully elaborated acyclic disulfide 2. The key segments 3 and 4, required for the preparation of the advanced key intermediate 2, were initially synthesized, and the two segments were subsequently subjected to the critical cross S-S coupling reaction to produce the desired key intermediate 11 (synthetically equivalent to 2). Upon deprotection of the N-Boc and the methyl ester groups in 11, the crucial cyclization formation was achieved using PyBOP to provide the desired macrolactam 16, a potential key precursor for 1. Further investigations concerning the transformation of 16 to the target molecule 1 were also described