Alkaloid moiety

Scheme 1.11. Diastereoselective synthesis of a Cgo-scandine conjugate by tandem reaction sequence involving a photoinduced addition of a tertiary amine and a [2 + 2] cycloaddition. The structure of the product includes a noninherently chiral functionalization pattern in addition to stereogenic centers in the alkaloid moiety.

Drawing from their success with catalytic [4 + 2] cycloaddition, Lectka group developed another highly enantioselective cycloaddition of o-quinone methide (o-QM) with silyl ketene acetals, using a chiral cinchona alkaloid derived ammonium, N-(3-nitrobenzyl)quinidinium fluoride Is, as a precatalyst. The free hydroxyl group of the cinchona alkaloid moiety was crucial to high optical induction. A variety of silyl ketene acetals had been screened to afford the cycloadducts 22 with good ee (72-90%) and excellent yield (84—91%) (Scheme 10.26) [35]. 

Further studies by Lindner and Maier have shown that substitution of one of the cinchona alkaloid moieties in dimeric cinchona phthalazine-type CSPs with a bulky naphthalene group still allows to maintain the high enantioselectivity of separation. For example, enantioseparation of DNZ-protected P-neopentylglydne on mixed CSP 63 occurs with excellent selectivity, a = 34.2 [106]. 

This proposal was later refuted by Kolb et al. [65] based on the fact that the rate of the AD reaction is first order in both osmium tetroxide and alkene, while Corey s proposal would require a second-order component for osmium tetroxide. Furthermore, Kolb et al. showed that the second alkaloid moiety in the bis-alkaloid ligands is not necessary for high enantioseiectivity, precluding any interaction between both quinuclidine nitrogen atoms and osmium tetroxide. The two prevalent models for explaining the introduction of enantioseiectivity in the AD process both operate with one active osmium tetroxide molecule per ligand. 

The 2,4,5-trimethylpyrrole-3-carboxylic acid ester of ephedrine has been synthesized by a mixed-anhydride procedure mild enough to leave intact the acid-labile pyrrolecarboxylic acid as well as the alkaloid moiety. 

Outside these two families, however, no other plants have been found to produce real tetrahydro-, dihydro-, and fully aromatic isoquinoline alkaloids in a polyacetate way. Closely related, but chemically a lactam, is siamine (40) from Cassia siamea Lam. (Leguminosae) (42). The structure suggests a biogenesis from a pentaketide precursor 41 (Fig. 2), thus requiring one acetate unit less than each of the naphthyl isoquinoline alkaloid moieties. 

In 2012, Zhang and coworkers [123] synthesized interesting hexahydropyrroloindole alkaloids (moieties that appear in a wide selection of alkaloids and drug candidates) using a highly useful copper-catalyzed intramolecular arylation-alkylation of o-bromoanilides (Scheme 8.72). 

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