Chiral building blocks alkaloids

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

In 2008, Lhommet and co-workers, by extrapolation of a previously described polycyclic version [144], proposed the three-component condensation of acrolein, (5)-2-phenylglycinol, and various acyclic 1,3-dicarbonyls in toluene in the presence of 4 A molecular sieves for the preparation of chiral, bicyclic functionalized tetrahydropyridines (Scheme 50) [145]. These heterocycles may be used as chiral building blocks for the synthesis of alkaloids, as illustrated by the total enantiose-lective synthesis of (—)-lupinine in five steps and 29% overall yield. 

The chiral lactone (178) has been used for the synthesis of a variety of natural products, such as sugars, lignans, terpenes, alkaloids, and P-lactams as a chiral building block 182c,184). The use of (178) as a powerful inductor of asymmetry was mainly established by Takano et al. 181, 84> one can expect more highly interesting reports from this group. 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

SYNTHETIC STUDIES ON BIOLOGICALLY ACTIVE ALKALOIDS STARTING FROM LACTAM-TYPE CHIRAL BUILDING BLOCKS... 

Finally, the type IV chiral building block 15 was synthesized via the iminium reduction of the corresponding iminiun salt derived from the vinylogous urethane 14 as shown in Scheme 5. With all four stereoisomers of the chiral building blocks (I IV) for synthesis of 3-piperidinol alkaloid in hand, we examined the synthesis of prosafrinine,... 

Davis and Andermichael recently described a new method for the asymmetric synthesis of 3-substituted-1 -(2//)-isoquinolones which are important chiral building blocks for alkaloid synthesis.83 This procedure involved the highly diastereose-... 

However, there has been no report on the highly stereoselective chiral synthesis of (- )-trachelanthamidine (100a) and ( + )-epilupinine (enr-lOOd) type alkaloids without the use of a chiral building block, except for Takano s chiral synthesis (33% optical purity) (81H(16)915),... 

Roush, W. R. An asymmetric intramolecular Michael reaction. Construction of chiral building blocks for the synthesis of several alkaloids. Chemtracts Org. Chem. 1988,1, 233-235. 

Synthetic Studies on Biologically Active Alkaloids Starting from Lactam-Type Chiral Building Blocks... 

The hetero [2+2] cycloaddition reaction is a synthetically important reaction for the construction of 4-membered heterocyclic compounds. As far as the catalytic asymmetric reaction is concerned, however, only the cycloaddition between ketenes and aldehydes has been reported. The thus synthesized chiral oxetan-2-ones are employed as monomer precursors for the biologically degradable co-polyesters and also as chiral building blocks for natural product synthesis. Two types of catalysts. Cinchona alkaloids and a chiral Lewis acid, are known to promote this reaction. 

Synthesis of new 3-piperidinol-type chiral building blocks and their application to the alkaloids syntheses 99YGK1075. 

An enantioselective total synthesis of (+)-ptilocaulin (79), a marine alkaloid with high antimicrobial and cytotoxic activity, was reported by Schmalz (Scheme 14) [40, 41]. The synthesis starts from anisole-Cr(CO)3, which is converted to the planar-chiral building block 74 with >99% ee by enantioselective deprotonation/silylation [42] and subsequent recrystallization. After attachment of a 2-butenyl side-chain ( 75) [43], nucleophilic addition of 2-lithio-l,3-... 

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