Total asymmetric transformation

Weissbuch, I., Addadi, L., Leiserowitz, L., and Lahav, M. Total asymmetric transformations at interfaces with centrosymmetric crystals role of hydrophobic and kinetic effects in the crystallization of the system glycine/ a-amino acids. J. Amer. Chem. Soc. 110, 561-567 (1988). 

The asymmetric polymerization in crystalline architectures provides an excellent environment to conduct the absolute asymmetric synthesis of polymers, and also provides an effident route for the ampHfication of chirality. Mirror-symmetry breaking might occur either through total asymmetric transformations, either in enantiomorphous crystals that have self-assembled from achiral molecules, or within racemic crystalline architectures which are delineated by chiral rims or surfaces when one of the chiral faces is blocked by an interface. The self-assembly of nonracemic mixtures into a mixture comprising eutectic compositions of a racemic compound and an enantiomorphous assembly, followed by asymmetric transformation, provides a series of thermodynamically controlled, alternative routes for the effident ampHfication of homochirality. 

The legioselectivity of electrophilic additions of the C=C double bond in 7-oxabicyclo[2.2.1]hept-5-en-2-yl (7-oxanorbom-5-en-2-yl) derivatives depends on the nature of the substituents at C(2). The adducts so-obtained can be transformed into the corresponding 5,6-disubstituted 7-oxanorboman-2-ones, which can be mono-substituted at C(3) stereoselectively, giving products with the same stereochemical information as hexoses. Thus, optically pure 7-oxanorbom-5-en-2-yl derivatives can be viewed as "naked sugars" Applications to the total, asymmetric syntheses of L-daunosamine, 2-deoxy-L-fucose, D- and L-aUose, D- and L-talose, D- and L-ribose,... 

In 1985, Vasella and co-workers provided an efficient synthesis of COTC ((4R,5R,6R)-2-crotonyloxymethyl-4,5,6-trihydroxycyclohex-2-enone 52), a gly-oxalase I inhibitor.Methyl a-D-mannopyranoside was transformed in three synthetic steps into the protected all cis-trihydroxycyclohex-2-enone 163 (34 %, overall) which was then transformed into COTC (52) in four steps. Thus, transformations of our "naked sugar" 32 to 137 — 138 — 163 realize a total, asymmetric synthesis of COTC. Another total synthesis of this natural compound has been reported recently by Koizumi and co-workers, as mentioned earlier. 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

A dynamic kinetic asymmetric transformation (DYKAT) of racemic vinyl aziridine 347 yielded the enantiopure imidazolidinone 348 (Scheme 90) <20050L823>. This transformation was the initial step in a total synthesis of (+)-pseudodistomin D. 

A practical and total spontaneous resolution process for the asymmetric transformation of ( )-narwedine (269) into either of its enantiomers, depending on which enantiomer is used as the seeds, and a highly stereospecific conversion of (-)-narwedine (269) into (-)-galanthamine (261) by reduc-... 

Shieh WC, Carlson JA (1994) Asymmetric transformation of either enantiomer of narwedine via total spontaneous resolution process, a concise solution to the synthesis of (—)-galantha-mine. J Org Chem 59 5463-5465... 

One good example of the application of this technology is in the AAA reaction of a racemic vinyl epoxide. The epoxide undergoes a dynamic kinetic asymmetric transformation (DYKAT) by reaction with p-methoxybenzyl alcohol, the standard ligand, and a palladium source. The product is obtained in 69% yield and 98% e.e. After further manipulations a key building block for the nonpeptidic protease inhibitor tipranavir was produced. Coupling of this intermediate with a synthon obtained using a molybdenum-catalyzed DYKAT process led to an advanced intermediate in a total synthesis of tipranavir (Scheme 20.14). ... 

Trost BM, Toste FD (2003) Palladium Catalyzed Kinetic and Dynamic Kinetic Asymmetric Transformations of y-Acyloxybutenolides. Enantioselective Total Synthesis of (-) Aflatoxin Bl and B2a. J Am Chem Soc 125 3090... 

In addition, the same group has studied the ability to use aliphatic alcohols as competent nucleophiles in the Pd-catalysed dynamic kinetic asymmetric transformation of Baylis Hillman adducts. The corresponding substituted pyran products were obtained in high yields and enantioselectivities, as shown in Scheme 2.55. The utility of this method was further demonstrated in the context of concise total syntheses of the gastrulation inhibitor, (-l-)-hippo-spongic acid A, and the antibiotics, furaquinocins A, B and E. 

Bonner concluded that efficient polymerization mechanisms that involve enantiose-lective enrichment via a-helix or /3-sheet secondary structures during polypeptide growth, are applicable to prebiotic environments. Total spontaneous resolution of racemates during crystallization involving secondary asymmetric transformations can also be important. The polymerization amplification concept involves the partial polymerization of a slightly enriched amino acid mixture, followed by an autocatalytic sequence of additional partial hydrolysis and polymerization steps. These amplification reactions occur because reactions of one enantiomer with another to form two diastereomeric products occur at different rates for each diastereomer. 

Allylation of carbonyl compounds is another very useful carbon-carbon bond forming asymmetric transformation in organic synthesis. This transformation yields the homoallylic alcohols that have proven to be valuable reagents and intermediates that have found numerous applications in natural product total synthesis. In particular, asymmetric allyl-boration of aldehydes employing tartrate- and pinane-derived reagents has been widely exploited. Although the asymmetric allylation reaction is well documented and widely used in solution phase, the asymmetric variant of the allylation of carbonyl compounds on the solid support has remained largely unexplored. ... 

MacMillan s group demonstrated that iminium catalysis can be a general and reliable strategy for organic synthesis by employing the imidazolidinone-type catalysts successfully in a wide range of asymmetric transformations [10,12], One example is the total synthesis of the more complex natural product (-t-)-minfiensine, which was isolated from Strychnos minfiensis (Scheme 3.2) [17], Due to its unique structure and potential biological activity, (-i-)-minfiensine has also attracted considerable attention... 

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

This type of asymmetric conjugate addition of allylic sulfinyl carbanions to cyclopen-tenones has been applied successfully to total synthesis of some natural products. For example, enantiomerically pure (+ )-hirsutene (29) is prepared (via 28) using as a key step conjugate addition of an allylic sulfinyl carbanion to 2-methyl-2-cyclopentenone (equation 28)65, and (+ )-pentalene (31) is prepared using as a key step kinetically controlled conjugate addition of racemic crotyl sulfinyl carbanion to enantiomerically pure cyclopentenone 30 (equation 29) this kinetic resolution of the crotyl sulfoxide is followed by several chemical transformations leading to (+ )-pentalene (31)68. 

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