Alkaloid from aldehydes

Positively activated olefins have also been condensed with dienamines derived from aldehydes 321,330,347,348) and ketones. Of special interest is the formation of bridged systems from homoannular dienes (229-231) which has been applied to the isoquinuclidine system of the iboga alkaloids (137-140,349). 

Scheme 35. Biosynthesis of benzo[c]phenanthridine alkaloids from protoberbines via the enamine aldehydes 193.

A biomimetic synthesis of benzo[c]phenanthridine alkaloids from a protoberberine via the equivalent of a hypothetical aldehyde enamine intermediate has been developed (130,131). The enamide 230 derived from berberine (15) was subjected to hydroboration-oxidation to give alcohol 231, oxidation of which with pyridinium chlorochromate afforded directly oxyche-lerythrine (232) instead of the expected aldehyde enamide 233. However, the formation of oxychelerythrine can be rationalized in terms of the intermediacy of 233 as shown in Scheme 41. An alternative and more efficient... 

The allenylsilane ene reaction is also well suited for the synthesis of cyclohexane rings. Jin and Weinreb have described the process of Eq. 13.55 in a synthesis of 5,11-methanomorphanthridine, an Amaryllidaceae alkaloid [64], Conversion of aldehyde 163 to imine 164 with piperonylamine took place in situ. Heating the solution of imine at reflux in mesitylene for 2 h led to cyclization through the conformer shown. The yield of 165 from aldehyde 163 was 66%. 

Lee, D.-U., Shin, U.-S. and Huh, K. 1996. Inhibitory effects of gagaminine, a steroidal alkaloid from Cynanchum wilfordi, on lipid peroxidation and aldehyde oxidase activity. Planta Medica, 62 485-487. 

If there are heteroatoms in the molecule, the [1,3] shift can be catalysed by acids or Lewis acids. The heterocycle 49, needed for a synthesis of alkaloids from narcissi, is formed from the cyclopropyl imine 48 with HBr catalysis.12 The imine 48 comes from an aldehyde 47 made in the same way as 43. 

The mammalian alkaloids are formed from aromatic amino acids and their metabolically derived amines by reaction with carbonyl substrates at physiological pH. The reaction is catalyzed by acid and is commonly referred to as the Pictet-Spengler cyclization (I0a,b,II). Winterstein and Trier in 1910 proposed that the Pictet-Spengler reaction might be of significance in the biosynthesis of benzylisoquinoline alkaloids in plants (5a). The carbonyl compounds participating in the Pictet-Spengler synthesis of mammalian alkaloids are aldehydes and a-keto acids, which are produced... 

The microwave-assisted synthesis of indeno[l,2-h]pyridmes 12 and 13 have been reported by Tu and co-workers [63]. The 5//-mdeno[l,2-h]pyridin-5-one framework is present in the alkaloids from Annonaceae species that represent a small but biologically intriguing group of compounds [64, 65]. Applying a micro-wave-assisted MCR with a suitable aldehyde, an acetophenone, a 1,3-indanedione or a 1 -indenone and ammonium acetate in DMF, a small library of compounds 12... 

REISSEBT - GROSHEINTZ - FISCHER CyanoaimneReaction Synthesis of aldehydes or alkaloids from acid chlorides via 1 ano-2-acynsoquinoime or 2-eyanoquinohne Intermediates... 

The efficiency of secondary amine catalysts is often eroded when moving from aldehydes to ketones as the donor carbonyl substrates, a trend that can be explained in terms of either the greater difficulty in the generation of the intermediate enamine species or their attenuated reactivity. To alleviate this situation, primary amines have emerged as a complementary family of amine catalysts. For instance, proline and related chiral secondary amines are not useful catalysts for the a-amination of aromatic enolizable ketones. As in other similar situations involving ketones as substrates, primary amines proved to be superior catalysts, although in these cases the presence of an acid co-catalyst seems to be crucial for reactivity. For instance (Scheme 11.4), primary amines derived from cinchona alkaloids can efficiently... 

---