Preparation of chiral building blocks

Tietze, L.F. and Gorlitzer, J., Preparation of chiral building blocks for a highly convergent vitamin E synthesis. Systematic investigations on the enantioselectivity of the Sharpless bishydroxilation. Synthesis, 1998, 873. 

Preparation of Chiral Building Blocks by Biochemical Methods... 

Taniguchi, T, Ohnishi, H, Ogasawara, K, An expedient preparation of chiral building blocks having levoglucosenone chromophore a new enantiocontrolled route to (—)-p-multistriatin and (+)-exo-brevicomin, Chem. Commun., 1477-1478, 1996. 

Hydrolases have also been used in synthetic applications, primarily for the preparation of chiral building blocks (Secundo and Carrea, 2003). The usage of organic conditions allowed the solubilization of the substrate, increased thermal stability and the prevention of water dependent side reactions. 

W. Wostl, Large scale preparation of chiral building blocks for the P3 site of renin inhibitors, Bioorg. Med. Chem. 1994, 2, 403-410. 

Scheme 6.10. Top Some of the possible paths for the preparation of chiral building blocks for the assembly of substrates for a [2,3]-Wittig rearrangement.

For the synthesis of carotenoids in optically active form, compounds ex chiral pool have been used extensively as starting materials, the synthesis of capsorubin (413) from (+)-camphor being one of the most prominent examples (see Chapter 3 Part ni.E). In the following examples, the preparation of chiral building blocks for the synthesis of chiral carotenoids starting from an amino acid and a terpene is described. 

Oiganocatalyzed enantioselective desymmetrization of diols in the preparation of chiral building blocks 12CEJ13920. 

Renaud P, Seebach D (1986) Preparation of chiral building blocks from amino acids and peptides via electrolytic decarboxylation and TiC -induced aminoalkylation. Angew Chem Int Ed Engl 25 843-844... 

If easy access is accompanied by synthetic flexibility and high optical purity of the compounds involved, this can amount to the directed and predictable preparation of chiral building blocks, as demonstrated for enamine 609 [228]. 

Nitrenes and nitrenoids are relative newcomers on the synthesis stage as well-behaved intermediates for stereoselective bond construction. Recent advances in nitrene chemistry provide exciting new tactics for the preparation of chiral building blocks. Consequently, in addition to transformations in-... 

Francotte, E. and Wolfe, N., Preparation of chiral building blocks and auxiliaries by chromatography on cellulose triacetate (CTA I) indications for the presence of multiple interaction sites in CTA I, Chirality, 2, 16-31, 1990. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Chiral Building Blocks Some drugs are made using chiral building blocks to generate the required chiral center in the drug. The introduction of chiral centers ensures that the reaction proceeds in the desired direction. The preparation of enalapril, an ACE inhibitor, is an example of the use of chiral building blocks. 

As seen in Section 1.3.4.1 (synthesis of lotrafiban), the recycling of an unwanted enantiomer resulting from a kinetic resolution allows theoretical yields of up to 100% to be achieved, but it can also create a bottleneck in a production process. DKR, where a starting material undergoes racemization in situ, either spontaneously or through the action of a second catalyst, offers a more efficient approach. This technique has been applied, particularly in academia, to the preparation of a broad range of chiral building blocks, and a number of recent reviews are available. 

Electrolysis of A-carbamoylaspartic acid or A-ethoxycarbamoylaspargine in MeOH-MeONa-(C) affords the corresponding methoxylated products [140], A 5-fluorouracil derivative (LXIII), a potent antitumor agent, can be prepared via electrolytic methoxylation of A-acylazacycloalkane-2-carboxylic acids (LXI) in MeOH-MeONa-(C) and subsequent condensation of (LXII) with 2,4-bis-(trimethylsilyl)-5-fluorouracil (TMS-5-FU) [Eq. (31)] [133,141]. Recently, the decarboxylative methoxylation of o -amino acids has been extended to prepare useful chiral building blocks [127-130]. 

Preparation and exploitation of chiral building blocks having a di-oxabicyclo[3.2.1]octane framework 02YGK317. 

The enantiomerically enriched 4-hydroxyenones 32 are an important class of chiral building blocks. This class of molecules has generally been obtained by the enzymatic or nonenzymatic catalytic desymmetrization of meso-cyclic diols 31 (or their derivatives) that can be prepared from the meso-endoperoxides 30 [32]. It is also well known that achiral bases such as NEt3 can promote the Kornblum-DeLaMare rearrangement of the meso-endoperoxides 30 [33]. This process is believed to proceed via the E2... 

Discovery and optimization of peptide and peptidomimetic therapeutics generally requires ready access to a diverse range of chiral building blocks. The DuPHOS-Rh catalysts provide one of the most convenient routes to novel amino acids, yet individual a-enamides must be prepared for each new amino acid needed. In an effort to enhance the efficiency of our hydrogenation methodology, we have developed a two-step tandem catalysis procedure for preparation of a wide range of aromatic amino acids and peptides (Scheme 7) [16,17,24]. 

The Cr(salen)-catalyzed ARO could be applied to prepare a range of chiral building blocks useful for the synthesis of biologically important compounds. Practical routes to cyclic cis- and trans-l,2-amino alcohols have been developed using Cr(salen) catalysis [11]. ARO methodology also enabled the enantioselec-tive synthesis of the core structures of balanol [12], prostaglandin derivatives... 

The Seebach aglycone synthesis is also independently based on the aldol coupling of the dialdehydic diolide 282 and the ethyl ketone 288, which are prepared by the use of chiral building blocks, Roche ester 285 or diethyl (S)-malate (286) and ethyl (R)-3-hydroxybutyrate (287). 

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