Seco acids

According to Quinkert, photoexcited cyclic ketones may be transformed to open-chain unsaturated carboxylic acids in the presence of molecular oxygen. This reaction may compete efficiently with a-cleavage and secondary transformations thereof. Thus, both stereo iso meric 17-ketones (109) and (110) yield as much as 20% of the unsaturated acid (111) when irradiated in benzene under a stream of oxygen. This photolytic autoxidation has been used notably for partial syntheses of naturally occurring unsaturated 3,4-seco-acids from 3-oxo triterpenes (for references, see ref. 72). 

Oxidation of 17j5-acetoxy-5a-androstan-3-one (1) by chromium trioxide in acetic acid at 55-65° gives the 2,3-seco acid (2). Conversion of the seco acid to its anhydride followed by pyrolysis and distillation gives the A-nor-2-ketone (3) in 45% overall yield. Analogous reactions have been carried... 

P-Acetoxy-A-nor-5a-androstan-2-one (3). A solution of 50 g of seco acid (2) and 70 ml of acetic anhydride is heated at reflux temperature for 2 hr. 

Oxidative rearrangement of 5a-cholestan-3-one (62) with hydrogen peroxide and a catalytic amount of selenic acid affords 2a-carboxy-A-nor-5a-cholestane, isolated in about 35 % yield as the methyl ester (63)." However, the reaction gives a complex mixture of A-nor- and seco-acids, and under... 

Sorm" " found that when cholesterol acetate (67) is oxidized by chromic acid in acetic acid-water at 55°, crystalline keto seco-acid (69) is obtained in 25-30 % yield from the mother liquors after removal of successive crops of 7-ketocholesterol acetate (68). Reaction of keto acid (69) with benzoyl chloride in pyridine gives a dehydration product, shown" to be the )5-lactone... 

An excellent alternative route to 5,6-seco-acids of general structure (69) has been used by Knof to prepare B-norsteroids. Although the single-step chromium trioxide oxidation process described in section III-A is convenient when starting materials are readily available and relatively low yields are acceptable, the multistep Knof process may be preferred when high yields are important or when a sensitive functionality is present. 

Synthesis of Seco Acid 4 and Completion of the Total Synthesisof Cytovaricin... 

Elaboration of triol 88b to bryostatin 7 requires chemoselective hydrolysis of the Cl methyl ester in the presence of the C7 and C20 acetates, macrolide formation, installation of the C13 and C21 methyl enoates, and, finally, global deprotection. The sequencing of these transformations is critical, as attempts to introduce the C21 methyl enoate to form the fully functionalized C-ring pyran in advance of macrolide formation resulted in lactonization onto the C23 hydroxyl. In the event, trimethyltin hydroxide promoted hydrolysis [73] of the Cl carboxylate of triol 88b, and subsequent trie thy lsilylation of the C3 and C26 hydroxyls each occurs in a selective fashion, thus providing the seco-acid 89. Yamaguchi macrolacto-nization [39] proceeds uneventfully to provide the macrolide 67 in 66 % yield (Scheme 5.14). 

Synthesis of the macrolide 6-deoxyerythronolide B 28 is one of the successful demonstrations of double asymmetric induction applied to the construction of complicated natural products.5 Retro synthetic analysis (Scheme 7-7) shows that 28 can be obtained from thio-seco acid 29, which consists of seven propionate building blocks. This is a typical aldol product in which a boron reagent... 

Scheme 7-9. Synthesis of a derivative of the seco acid and ring closure to 6-deoxyerythronolide B.

A stereoselective osmylation approach was applied to the synthesis of C(l)—C(7) and C(7)—C(13) subunits of erythronolide A41. A key synthon of the erythronolide A seco acid, 30, was prepared in an enantiomerically pure form by utilizing a stereoselective osmylation of the chiral hydroxy (Z, )-diene ester 31 and subsequent hydrogenation of the resulting butenolide 32 (equation 24). 

Erythronolide A (8) is a 14-membered macrolide, with ten chiral centres. Because a 14-membered ring is not only as flexible as a linear open-chain, but also prone to experience several kinds of transannular interactions, any kind of stereochemical control must be exerted in the corresponding open-chain derivative,20 i.e. in the seco-acid 9, or in the linear fragments resulting from its disconnection, which should be immobihsed or "frozen" in someway. 

Disconnection of the seco-acid M into fragments A and B, as shown in Scheme 9.26, immediately suggests the order in which the aldol condensations must be effected to arrive at the target molecule. 

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