Vitamin synthetic approaches

The first synthesis of vitamin IQ was reported by several workers ia the late 1930s and the synthetic approaches have been reviewed (22). Vitamin IQ was prepared by the reaction of menadione with phytyl bromide ia the preseace of 2iac (23). 

The important biological role of the isobacteriochlorins has decisively influenced the development of synthetic approaches leading to the isobacteriochlorin class of compounds. All of the naturally occurring isobacteriochlorins contain geminally dialkylated structural parts in the saturated pyrrole rings, which require special approaches for their synthesis. Until the discovery of siroheme and sirohydrochlorin, this structural element could only be found in vitamin B,2. Using the synthetic potential, which was invented during numerous syntheses of... 

This knowledge subsequently initiated much work in isolating new natural pteridines as well as many synthetic approaches to this heterocyclic nucleus as exemplified by the vitamin folic acid and methotrexate, an antileukemia drug <49JA1753>. The importance of this interdisciplinary field was recognized as early as 1952 by Polonovski, who organized the first symposium. By 1995, 10 periodic international congresses and many more symposia on specific aspects of pteridines followed. 

The examples discussed in this paper demonstrate that Pd-catalyzed coupling reactions can be successfully utilized in the convergent (modular) synthesis of vitamin D-active compounds. The new synthetic routes open an efficient and highly selective access to a variety of vitamin D analogs. While reliable methods exist today for the construction of the triene system and for the synthesis of the ring A precursors, the search for efficient total synthetic approaches to the CD building blocks still remain a challenging task for the future. 

Totally synthetic approaches to vitamin D and its relatives are presented in the Simonsen lecture.180 Two syntheses of 25,26-dihydroxycholecalciferol have been reported and establish the 255-configuration for the natural metabolite,181-182 and the 25i -configuration182 for the previously synthesized 25,26-dihydroxycholesterol,... 

A variety of established industrial processes for the manufacture of and new synthetic approaches to certain optically active compounds such as pharmaceuticals vitamins, and fine chemicals are surveyed. Among the techniques for obtaining optically pure intermediates covered in this review are classical or modified optical resolutions, the utilization of starting materials from the chiral pool, as well as stoichiometric and catalytic asymmetric transformations. 

The development of a practical total synthesis of natural (2R,4 R,8 R)-a-tocopherol ( ) is a major challenge. While much progress has been made in this area, a technically feasible synthetic approach to this form of vitamin E remains an elusive goal and Isolation from soybean oil continues to be the major... 

In order to assess the importance of the 3-hydroxy I group with respect to vitamin D activity, 3-deoxy-l-hydroxylated analogs have been synthesized from steroidal precursor [scheme (20)] and by the total synthetic approach of Okamura... 

A second well-known sulfur-containing coenzyme is biotin Biotin, a member of the B vitamin complex, plays an essential nutritional role in carboxylation reactions. It is the coenzyme of carboxylases and catalyzes fundamental metabolic processes. Its relative unavailability from natural sources spurred great interest in synthetic approaches, the most recent of which appeared in xhe synthesis of... 

The Leeds synthesis of vitamin D3 requires too many steps to be commercially interesting. All the same, the Horner-Wittig connection of the two building blocks containing ring A, or rings C and D, respectively, played a not inconsiderable role in the total synthesis of the vitamin-D metabolites 13 and 14 ). Scheme 15 [31] summarizes various synthetic approaches in this area... 

The isolation of the active metabolites of vitamin D from biological tissues is extremely laborious and affords only small quantities of material. Development of synthetic approaches to these materials was thus necessary to provide them and related analogs in adequate quantity for elucidation of their mode of action. The new chemistry required was that in which new functionalities, usually hydroxyl groups, could be... 

These medical needs have renewed interest in the development of short and flexible synthetic approaches to clinically usable vitamin D3 analogues. The procedure described here is a convenient preparation of a key precursor in the s3mthesis of la,25-dihydroxyvitamin D3. In this representative procedure, sonication of a mixture of 1, methyl vinyl ketone, Zn, and Cul, in aqueous EtOH (70% v/v) at room temperature affords ketone 2 in 73% jdeld. A control experiment without sonication indicated no progress of the reaction after stirring for 26 h. 

Abstract The in vitro enzyme-mediated polymerization of vinyl monomers is reviewed with a scope covering enzymatic polymerization of vitamin C functionalized vinyl monomers, styrene, derivatives of styrene, acrylates, and acrylamide in water and water-miscible cosolvents. Vitamin C functionalized polymers were synthesized via a two-step biocatalytic approach where vitamin C was first regioselectively coupled to vinyl monomers and then subsequently polymerized. The analysis of this enzymatic cascade approach to functionalized vinyl polymers showed that the vitamin C in polymeric form retained its antioxidant property. Kinetic and mechanistic studies revealed that a ternary system (horseradish peroxidase, H2O2, initiator fS-diketone) was required for efficient polymerization and that the initiator controls the characteristics of the polymer. The main attributes of enzymatic approaches to vinyl polymerization when compared with more traditional synthetic approaches include facile ambient reaction environments of temperature and pressure, aqueous conditions, and direct control of selectivity to generate functionalized materials as described for the ascorbic acid modified polymers. 

Based on initial studies of Mazur, method B for the production of vitamin D metabolites and analogs has been nicely developed by several groups. In the Mazur approach, the vitamin D isomerized to the i-steroid 191, which can be modified at carbon C-1 and then subsequently back-isomerized under solvolytic conditions to afford la,25-dihydro-xyvitamin D3 or analogs. The studies presented here led to the separate production of bicyclo[3.1.0]hexane derivatives 192 in a chemoenzymatic synthetic approach to 191. 

In developing synthetic strategies for macrocycles related to corrins, one initial choice has to be made, i.e. whether to incorporate the direct link between rings A and D or to generate it in the final cyclization step. Examples of both approaches have been reported, but syntheses in which the direct link is formed in the final cyclization are more numerous. The total syntheses of vitamin B12 by Woodward/Eschenmoser and Eschenmoser are prominent examples for the realization of both strategies. 

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