Stereochemistry, biosynthesized

Hybridalactone, a novel marine derived eicosanoid from Laurencia hybrida, appears to be biosynthesized by a unique pathway from eicosapentaenoic acid. The synthesis of hybridalactone was carried out enantiospecifically from (+)-bicyclo[3.2.0]hept-4-ene-l-one so as to provide proof of stereochemistry (Ref. 4). 

Comparison of the structures of the Lasioderma compounds 121 and 122 with the Stegobium compounds 123 or 124 reveals strong similarities even with respect to the stereochemistry. The biosyntheses may be very similar involving a C3-unit as the stereotypic building block. As already mentioned above (see introduction and Fig. 2) the skeletons of 123 and 124 would be formed when the methylmalonate (or propanoate) unit terminating the chain elongation of 121 and 122 would be replaced by malonate (or acetate), respectively. 

Two epimeric amino alcohols, 2(5)-aminotetradeca-5,7-dien-3(5)- and -3(/ )-ol (305 and 306) were isolated from a sponge from Papua New Guinea (Xestospongia sp.) (248). The absolute stereochemistry was disclosed by degradation to L-alanine, and these amino alcohols (305 and 306) were suggested to be biosynthesized from fatty acids and alanine. Compounds 305 and 306 show antimicrobial activity. Rhizochalin (307) was isolated from the Madagascan sponge Rhizochalina incrustata as an antimicrobial constituent (349). The biosynthetic pathway for 307 is unknown but is conventionally believed to be derived from alanine and a polyketide precursors). 

The latter observation pointed to the question of the stereochemistry of the 3H atoms present at position 4 of vittatine biosynthesized from orfAo-labeled 3H 343. Previous work on haemanthamine (318) had shown that the degradations of oxohaemanthamine (407) and oxo-haemanthamine methiodide (408) prepared from 318 biosynthesized from [3, 5 -3H2 14C-O-methyl]0-methylnorbelladine leading to the diphenyl derivatives (409) and (410) possibly through the intermediacy of 407a and 408a proceeded with different 3H retentions 74 and 93%0, respectively. It seemed therefore that the protonation taking place in the conversion of the dienone (401) into noroxomaritidine (275) proceeded in a nonstereospecific fashion although further work is needed to settle the question completely (104). 

Figure 6.10 De novo biosynthesis of isoprenoid pheromone components by bark and ambrosia beetles through the mevalonate biosynthetic pathway. The end products are hemiterpenoid and monoterpenoid pheromone products common throughout the Scolytidae and Platypodidae (Figure 6.9A). The biosynthesis is regulated by juvenile hormone III (JH III), which is a sesquiterpenoid product of the same pathway. The stereochemistry of JH III is indicated as described in Schooley and Baker (1985). Although insects do not biosynthesize sterols de novo, they do produce a variety of derivatives of isopentenyl diphosphate, geranyl diphosphate, and farnesyl diphosphate. Figure adapted from Seybold and Tittiger (2003).

Incorporated as a dienophile. These results strongly indicate that dehydrogenation at the isoprenyl portion of (48) followed by a [4 2]cycloaddition reaction with the a, p-double bond of another molecule of isoprenylchalcone leads to the formation of the Diels-Alder type metabolites. Furthermore, the Diels-Alder type metabolites from the precursory chalcones (47), (48), and (53) are all optically active, having the same stereochemistries as those of )cuwanon J (11) and chalcomoracin (21). This fact revealed the [4 + 2]cycloaddition step to be enzymatic. Administration of O-methylated precursory chalcone to the M. alba cell cultures has thus demonstrated that optically active mulberry Diels-Alder type adducts such as 11 and 21 are biosynthesized through an enzymatic intermolecular [4 + 2Jcycloaddition reaction. 

Details of cholesterol biosynthesis continue to be explored. Further details of work concerning the stereochemistry of the rearrangement of the methyl group at C-15 of squalene (which migrates to C-13 of Ianosterol) during the biosynthesis of cholesterol by rat liver are available.Cholesterol, biosynthesized independently... 

The branched-chain amino acids valine, leucine, and isoleucine have very similar biosyntheses and catabolism. Valine 179 and leucine 205 have diastereotopic methyl groups and leucine 205 and isoleucine 212 have diastereotopic hydrogen atoms. These may be differentiated by labeling so that the stereochemistry of the biological processes involving these amino acids may be studied. 

The three aromatic amino acids that are biosynthesized in the shikimic acid pathway have much in common. The many stereochemical events occurring between the condensation of compounds 288a and 289 derived from carbohydrates to the formation of prephenic acid 296 have been extensively reviewed including a recent review by ourselves (82), and so we have summarized the stereochemistry of the biosynthesis in Scheme 79. Prephenic acid 296 leads to phenylalanine 297 and tyrosine 298. The mem-substituted amino acids 299 are derived from chorismate 295, as is tryptophan 302, as shown. 

The chirality of lutein (14) is now firmly established with the 3,3 -hydroxy functions in the P- and s-rings possessing opposite absolute configuration 4, 40). The stereochemistry of the hydroxylation step in zeaxanthin (26) biosynthesis in a Flavobacterium sp. has been determined by using (5/ )-[2- C, 5- Hi] mevalonate as substrate which demonstrated retention of the 5-pro-S hydrogen at C-3(3 ) (50), Scheme 9. Also in the case of lutein (14) it has been shown that the 5-pro-S hydrogen at C-3 is retained (81,171) and P,e-carotene (92) biosynthesized from (4/ )-[2- C, 4- Hi] mevalonate retains the tritium at C-6 (82). Any mechanistic interpretation of the biosynthetic evidence must be consistent with the established chirality. 

The stereochemistry of the formation of the double bonds in abscisic acid (36), biosynthesized by avocado fruit, has been studied using (2R)-[2- H]-, (2S)-[2- H]-, and (5S)-[5- H]-mevalonates. The anticipated stereochemistry of the hydrogen atoms derived from C-2 and C-5 of mevalonate is shown in (37). The C-3 and C-4 hydrogen atoms of abscisic acid (36) were derived from a 2-pro-R-mevalonoid hydrogen atom. The hydrogen atom at C-5 of abscisic acid is derived from a 5-pro-S-mevalonoid hydrogen. The presence of some label at positions 3 and 4 when (2S)-[2- H]mevalonic acid was the precursor was attributed to the action of isopentenyl isomerase. 

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