Chiral pool precursors

Total Synthesis Using Chiral Pool Precursors... 

Scheme 13.34 Chiral pool precursors for the C-8 stereogenic center of nonactic acid...

Soon thereafter, chirality was recognized as a necessary and indispensible part of synthetic receptor molecule design and function. Predictably, not only has nature s chiral pool been called upon to supply inexpensive and readily available sources of chirality, but the ability of the chemist to resolve optically active precursors from racemic modifications prepared in the laboratory has been exploited ingeniously in a number of different directions. The various elements of chirality centers, axes, planes, as well as helices, have been incorporated into both axially symmetric and asymmetric receptors. 

Carbohydrates are configurationally stable, easily available in enantiopure forms from the chiral pool, and they show a high density of chiral information per molecular unit. Their polyfunctionality and structural diversity fadhtate their tailor-made modification, derivatization, and structural optimization for a broad spectrum of synthetic applications. While derivatives of various saccharides have already been utilized as versatile starting materials and building blocks for chiral auxiliaries, ligands, and reagents [330] their obvious role as precursors for the... 

More recently, Mukai and Hanaoka have demonstrated that a variety of optically active bicyclo[4.3.0]-nones are prepared from the substrates possessing pre-existing stereogenic centers. The precursors are prepared from such a natural chiral pool as dimethyl L-tartarate or L-ascorbic acid (Equation (15)) S2,52a,52b... 

Since the stereochemical changes in each reaction of the sequence are known, a particular amino acid starting material (R or S) will give a particular configuration in the product. In this strategy of asymmetric synthesis, all or part of die final molecular skeleton is derived from the chiral precursor. While simple, diis strategy is limited by the size of the chiral pool and by the types of reactions which occur stereospecifically at tetrahedral centers. 

The most popular chemical entries to carbapyranosyl amines of the validamine subgroup exploit two major ouvertures, namely Diels-Alder annulation and ex-chiral pool-derived precursors homologation. 

These are (1) The chiral substrate approach. This approach involves using chiral precursors that transfer their chirality to the final cyclopentenone. This implies the synthesis of chiral substrates, which has generally been made from classic chiral pools. Examples include carbohydrate derivatives like 40 that give 41 with variable yields depending on the substitution pattern. 41 is transformed into cyclopenta[c]pyrane 42, which is the skeleton of iri-doids [93]. In another example epichlorhydrin (43) is used to construct chiral enyne 44 which gives cyclopentenone 45 [94] (Scheme 14). 

Starting from the chiral pool (/f-(+)-hmonene), the total synthesis of natural (-f)-3,4-epoxycembrene A (56) has been achieved by Liu et al. with the low-valent titanium-mediated intramolecular pinacol couphng of the corresponding sec-keto aldehyde precursor 171 (Scheme 6-25). A more general and efficient enantioselective synthesis of (+)-3,4-epoxy-cembrene A (56) with a chiral pool protocol and Sharpless asymmetric epoxidation for the introduction of three chiral centers has also been reported by the same authors in 2001 (Scheme 6-26). ... 

Amino acids are the monomers from which nature produces proteins and enzymes. As such, they form an important part of the chiral pool. Histidine contains an imidazole ring in the sidechain and thus is a logical target for the synthesis of functionalised and chiral NHC, Given that a primary amine, as found in natural amino acids, is a prerequisite for standard imidazole ring forming reactions [60], it is surprising that only a few protocols are found in the literature where an amino acid [61-66] or its respective alcohol [64,67] forms part of a reaction that leads to a carbene precursor,... 

To date, two total syntheses of myriaporone 4 are known. This chapter is based on the total synthesis of myriaporone 4 published by Taylor et al. in 2004. The synthesis of a chiral precursor, which has also been employed for the total synthesis of related compounds, was published by the same group in 1998. The linear total synthesis starts with an enantiomerically pure molecule from the chiral pool that delivers the stereogenic center at C-12 of the final product, employs Evans aldol reactions as key steps for stereoselective chain elongations and additionally includes reduction/oxidation steps as well as protecting group chemistry. 

This compound is a precursor to a Novartis drug used for the control of inflammation. How might it be made from a chiral pool starting material ... 

Rather than accessing the chiral pool via amino acid precursors for CBS catalysts, the (R,R)- and the (.S, -sulfonamide derivatives of 1,2-diphenyl- 1,2-diaminoethane... 

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