Acid-catalyzed biomimetic cyclization

Other approaches to the stereoselective total synthesis of nonaromatic steroids include the carbocationic, biomimetic cyclizntion reactions. Generally, these cyclizations begin with the synthesis of an appropriately functionalized cyclopentenol. Acid-catalyzed cyclization forms the B-C-D rings of the steroid nucleus with the natural relative stereochemistry in a single step. 

Despite extensive studies on acid-catalyzed diastereoselective polyene-cyclizations, their enantioselective behavior have not yet been reported. The stereochemical implications of polyene-cyclizations can be explained by the Stork-Eschenmoser hypothesis [140], and the most important feature required for an artificial cyclase is asymmetric induction during the initial protonation. Very recently, the author and Yamamoto et al. succeeded in the first enantioselective biomimetic cyclization of polypre-noids catalyzed by LB A [141]. 

Johnson, Corey, and van Tamelen have successfully utilized the biomimetic acid-catalyzed cyclization of polyolehnic substrates for the construction of steroids and some teipenes. Based on the previous work, Ireland and co-workers designed a route to the desired tetracycle 69 utilizing polyene cyclization (Scheme 12), which, although preparatively uncompetitive with the hydrocyanation (Scheme 11), was of some interest. Based on a model study, the symmetric dibromide... 

The chemical simulation of this biosynthetic process has been developed as an important methodology in organic synthesis. Van Tamelen reported the add-catalyzed cyclization of chiral terminal epoxides of polyprenoids [11]. In contrast, Johnson adopted the acid-catalyzed cyclization of poly-prenic acetals derived from chiral diols [12]. In addition to these pioneering studies, the biomimetic polyene cycliza-tions of polyprenoids, which are induced by a variety of electrophiles such as proton, oxonium ion, halonium ion [13], or metal ion [14], have also been developed. Despite extensive studies on these diastereoselective olefin cyclizations, enantioselective processes using synthetic chiral catalysts had not been developed for a long time. In 1999, Yamamoto s... 

The biomimetic-type cyclization of polyisoprenoids is an important industrial process for terpene synthesis. In most cases, a large excess of coned. H SO and SnCl. has been employed For example, ionone, a precursor of vitamin A, is prepared by coned. H2SO4 catalyzed cyclization of pseudoionone. The disadvantage of this process is undoubtedly the requirement of bases to neutralize the large excess of acid. The EGA method offers a promising alternative for this purpose. Thus, Electrolysis of 15 and 17 in a ClCHjCH Cl—LiClO —Et NClO — (Pt) system provides 16 and 18, respectively in reasonable yields and the neutralization of the reaction solution can be performed simply by addition of a small amount of pyridine... 

A biomimetic catechol cleavage reaction was carried out on dihydro-caffeic acid derivative 1922 using the iron(III)-catalyzed peracetic acid cleavage process of Pandell.25 This produced the cyclized muconic acid derivative 20 which could be transformed into pyrone 21 by treatment with hydrochloric acid. Bromination followed by azide displacement gave key intermediate 22 which could either be reduced directly to (i)-stizolobic acid 16 or ammonolyzed and then reduced to give ( )-3-(6-carboxy-2-oxo-4-pyridyl)alanine 17 (Scheme 4). 

An analogous biomimetic route to stizolobinic acid 15, the biosynthetic side chain precursor to acromelic acid A 5, was also carried out.23 Iron(III)-catalyzed peracetic acid cleavage of the catechol portion of 23 gave alanyl muconic acid 24 which was cyclized and concomitantly deprotected to (i)-stizolobinic acid 15 (Scheme 5). Use of Schollkopf bislactim ether methodology26 also allowed the formation of enan-tiomerically pure 15 by an analogous route. 

---