A Partial Synthesis of the Skeleton of Deoxypumiloside, a Putative Intermediate in Camptothecin Biosynthesis

Abstract

Ajmalicine (3) was used as the starting material for the synthesis of a camptothecin‐like skeleton. After C‐21 activation through allylic conjugation, regiospecific tertiary amine oxidation was achieved with mercury salts. Subsequent biomimetic oxidation of the indole nucleus then gave quinolone lactam 14. A two‐step process finally afforded 4, a close analogue of deoxypumiloside (5), one of the putative intermediates in the biosynthesis of camptothecin.

Asymmetric Approach to Hyacinthacines B1 and B2

“…After considerable experimentation, it was found that treatment of amino-nitriles 13 with LDA at low temperature, followed by addition of an excess of benzyl chloromethyl ether, gave the corresponding amino-nitrile 18 in high diastereomeric purity by NMR (Scheme ). For a successful alkylation, it was necessary to operate with rigorous exclusion of oxygen to avoid reversion of the substrate to lactam 12 . Although the crude product was not stable to purification, it could be smoothly reduced with sodium borohydride in methanol at 0 °C to afford uniquely the desired stereoisomer 19 in 49% yield (55% brsm, 2 steps).…”

Asymmetric Strecker Reactions

“…Another example of a highly stereoselective cyanide addition to the iminium salts is shown in Scheme . In the presence of KCN/citric acid, the iminium salt 55 derived from the heteroyohimbane alkaloid ajmalicine 54 underwent cyanide addition at room temperature to give the desired α-amino nitrile 56 with 72% yield and complete stereoselectivity …”

“…Although asymmetric Strecker reactions using chiral aldehyde- or ketone-derived imines can be found in many natural product syntheses of specific structures, this strategy tends to be extremely specific and highly structure-dependent. Hence, only those examples in which excellent chiral induction effects have been observed are used here to elucidate this particular strategy. − In contrast, the use of chiral optically pure amines as the chiral auxiliary for achieving the highly diastereoselective Strecker reaction has evolved into a relatively general and robust approach for accessing various enantiomerically pure α-amino acids. The performance of this strategic type of reaction requires stoichiometric amounts of chiral auxiliaries.…”

The Witkop-Winterfeldt-Oxidation of Indoles

“…Interestingly, unsubstituted derivative 124c furnished quinolone-imide 125c, presumably via CH-oxidation of the expected quinolone-amide intermediate (Scheme 28) [53]. Husson used their method for the synthesis of linear, pentacyclic pyrroloquinoline and pyrroloquinolone derivatives which resemble camptothecin [54][55][56].…”