Enantiodivergent synthesis

This suite of BVMOs is available via whole-cell expression systems and represents a complementary platform of biocatalysts for diverse applications in chiral synthesis. Representatives of this collection were utilized in the enantiodivergent synthesis of the indole alkaloids alloyohimbane and antirhine from a fused bicyclic precursor (Scheme 9.19) [151]. 

The diacetoxylation works well with a number of cyclic and acyclic conjugated dienes and has been applied to the synthesis of natural products33,34. For example, the meso diacetate from 2,4-hexadiene was used for the enantiodivergent synthesis of the carpenter bee pheromone343. 

Xenovinine 195, a natural alkaloid, was obtained by catalytic hydrogenolysis of carbamate 194 and subsequent intramolecular reductive amination of the in /-////-generated A-deprotected ketopyrrolidine <1999T8915>. Enantiodivergent synthesis of 195 with the same reductive amination as final step was also reported (Scheme 45) <1998EJO 955>. 

The required (R)- and (S)-P-hydroxysulfides were easily obtained from the same (/ )-epichlorhydrin through enantiodivergent synthesis (R = n-Bu in the scheme). 

F. Rulin, Microbial oxidation of chloro-aromatics in the enantiodivergent synthesis of pyrrolizidine alkaloids trihydroxyhelio-tridanes,/. Org. Chem. 1990, 55, 4683-4687. 

The latter reaction was further described by Koizumi et al. [86b] with slightly different results (lower facial selectivity for the exo-approach), in connection with the enantiodivergent synthesis of fused bycyclo [2,2,1] heptane lactones 91 (see Scheme 47). The key step of this transformation was the regioselective DIBAL reduction of only one of the two ester groups in the adducts, followed by... 

The pseudosymmetric acetate of Scheme 8-17 was employed in combination with the palladium-catalyzed reaction for the enantiodivergent synthesis of cis- and trans- 4-aminocyclohex-2-enol [72]. 

Scheme 8-17 Enantiodivergent synthesis of (2,4-cycloalkadien-l-yl)acetic acid.

An efficient enantiodivergent synthesis of levorotatory (lS,2/ ,8aS>l,2-dihydroxyindolia e (62a) and its antipode (62b) has been developed starting from commercially available o-isoascoibic acid (61 Scheme 27). This strategy illustrates the complementary use of iminium and IV-acyliminium ion inter-... 

Khiar, N., Singh, K., Garcia, M., Martin-Lomas, M. A short enantiodivergent synthesis of D-erythro and L-threo sphingosine. Tetrahedron Lett. 1999, 40, 5779-5782. 

Y. Nishimura, Y. Umezawa, H. Adachi, S. Kondo, and T. Takeuchi, Enantiodivergent synthesis and biological activity of mannostatin analogs, J. Org. Chem., 60 (1996) 480-488. 

Chiral monoesters, obtained either from a prochiral diol or diester, may be converted by a suitable series of chemoselective transformation to either enantiomer of a given target compound (enantiodivergent synthesis) (Scheme 11.1-13)110 40l... 

Barros, M.T., Maycock, C.D. and Ventura, M.R. (1997) Enantioselective total synthesis of (+)-eutypoxide B. The Journal of Organic Chemistry, 62, 3984-3988. The reaction in the presence of DBU (1 equiv.) was also reported Takano, S., Moriya, M. and Ogasawara, K. (1993). Concise enantiodivergent synthesis of eutypoxide B. Journal of the Chemical Society - Chemical Communications, 614—615. 

Carbopalladation products can be induced to undergo other reactions than /S-hydride elimination. For instance, carbopalladation products can undergo a second carbopalladation to form a second carbon-carbon bond. Such reactions have been termed polyene cychzations and have been exploited to construct the carbon skeletons of the scopadulcic acids (Scheme 26). Treatment of alkenyl iodide 165 under typical carbopalladation conditions induces a 6-exo carbopalladation onto the exo double bond. The resulting neopentylpalla-dium intermediate then undergoes a second 5-exo carbopalladation reaction followed by /3-hydride elimination dehvering tetracycle 166. Conversion of allyhc alcohol 166 to (—)-scopadulcic acid A 167 as well as analogous conversions in the enantiomeric series have lead to an enantiodivergent synthesis of both antipodes of the natural product. 

In the alkaloid domain, several hydroxylated alkaloids were chosen to demonstrate that arene cw-dihydrodiols can serve as synthons in heterocyclic synthesis. The first venture into this area was the enantiodivergent synthesis of pyrolizidine triols from erythruronolactone 30, as shown in Figure 8 (30-32). The same principles of enantiodivergent design of the pinitols were applied here to yield the two enantiomeric azido dienes 40 and 41, which were then transformed to the alkaloids by previously documented azide-diene cycloaddition followed by vinylaziridine- yrroline rearrangement (33). 

The enantiomerically pure monoacetate (w = 1) of Scheme 11.19 was employed in combination with a palladium-catalyzed reaction for an enantiodivergent synthesis of cis- and trons-4-amino-2-cyclohexenol [81]. 

In a separate communication, Kita and coworkers also reported an enantiodivergent synthesis of an ABODE ring analog of the antitumor antibiotic fredericamycin A via an intramolecular [4 + 2] cycloaddition. Late-stage oxidations were performed on the di-f-butylsilylene for protection of phenolic hydroxyl groups. Syntheses of both (R)- and (5)-enantiomers were reported (eq 18). ... 

Such a manipulation of cyclization reactions via bond rotation was also the key operation in an enantiodivergent synthesis of vinca alkaloids. 

The influence of the functional groups of the substrate in the course of an allylsilane addition to a carbonyl group are exempHfied in the enantiodivergent synthesis of the Geissman-Waiss lactone [63]. The Geissman-Waiss [64] lactone 200 and 202 serves as a versatile intermediate for the synthesis of pyrroUzidine alkaloids. For this reason, there are a variety of different syntheses to this building block [65]. The Geissmann-Waiss lactone synthesis of Wistrand and coworkers not only provides a short access to one enantiomer but also enables the synthesis of both enantiomeric forms. The synthesis is depicted in Scheme 3.40. 

Scheme 3.40 A short, enantiodivergent synthesis of the Geissman-Waiss lactone.

Recently, the same group reported two different epoxide hydrolases from Sphin-gomonas sp. and Solatium tuberosum with distinct stereopreferences that enabled enantiodivergent synthesis of diols in excellent yields and selectivities (Scheme 9.12) [74]. 

---