From 4-Methyl-3-hexenoic acid

Methyl-2-hexenoic acid (mixture of ll and Z isomers) has been identified as the substance responsible for the odor of human sweat. Synthesize the compound from starting materials having five or fewer carbons. 

The compound responsible for much of the underarm odor is 3-methyl-2-hexenoic acid in both its (E) and (Z) isomers (Zeng et ah, 1991). Breath can also communicate gender information. However as with axillary odor, breath from men tends to be classified as stronger and more unpleasant than that of women Doty etal, 1982). 

R)-Hydroxy-4-pentenoic44,322 (R-94) and 3(R)-hydroxy-3(R)-methyl-4-hexenoic (R-99, R = H)4S acids were obtained from the racemic acids by recrystallization of their quinine salts. Compound R-94 served322 as the substrate for the synthesis of 2-deoxy-L-eri/t/iro-pen-tose as in 94 —> 98. The enantiomeric acid R-99 was employed46 for the preparation of D-everniicose (see 99 — 105). 

Examples of 1,3-asymmetric induction in cyclizations to 8-lactones have been observed. Iodolactonization of 3-methyl-5-hexenoic acid to a 8-lactone under equilibrating conditions showed reasonable stereoselectivity (6 1 cis trans).l20b Recent studies have examined the formation of 8-lactones from cyclization of 5-hexenoic acids with a homoallylic oxygen substituent at C-3.135 Selenolactonization of 3-hydroxy-5-hexenoic acid under conditions of kinetic control provided the trans lactone in modest yield (40%) and high stereoselectivity.13515 Equilibrating conditions led to a slight preponderance of the cis... 

The iodocyclization of 4-methyl-5-hexenoic acid performed under conditions of thermodynamic control (iodine in acetonitrile in the absence of a base) leads to the preferential formation of the /raw.v-diequatorial 5-lactones (94 6) in 77% yield1. Similar results were observed starting from (S)-4-methyl-5-hexenoic acid (1), obtained from citronellol, with iodine in acetonitrile, followed by tributyltin hydride reduction. The 5,6-dimethylvalerolactone 2 was obtained in 40%) yield and 93.5 6.5 (irans/cis) diastereoselcctivity 2. 

The a-bromine atom is stable during lactone formation from a,y-dibromo-butyryl bromide the yield of a-bromo lactone is 94%. Under similar conditions the /3-bromine atom of /3,y-dibromohexanoic acid is eliminated as hydrogen bromide to give the lactone of 4-hydroxy-2-hexenoic acid. Cyclization of alkali salts of 15-bromopentadecanoic acid has been studied using various solvents and concentrations. Best yields of the O)-lactone are obtained from the potassium salt in methyl ethyl ketone. ... 

Evidence for such a modular pathway has been provided from studies into the biosynthesis of the polyketide backbone 77 of (41 )-4-[(E)-2-butenyl]-4-methyl-L-threonine 78 which is incorporated into cyclosporin A in Tolypo-cladium niveum [117]. The proposed biosynthesis of 77 is presented in Scheme 29. In vitro studies using a cell extract have verified unambiguously that the biosynthetic mechanism is processive, that the first PKS free intermediate is the tetraketide 79, and that methylation unequivocally occurs at the stage of the enzyme bound 3-oxo-4-hexenoic acid thioester 80 which is the triketide product from the second elongation cycle. These and other results indicate that the methyl transferase activity is inherent in the second module of the putative PKS. 

Methyl-2-hydroxy-5-hexenoic acid with 85%-H3P04 slowly distilled at 30 mm. —2,5-epoxy-2-methylhexanoic acid. Y 75%. (Bl. 1949, 24.) —Cyelization of sec. alcohols is best effected by H3P04, which, however, forms diethylenic hydrocarbons from tert. alcohols (Bl. 1949, 17). (F. e., also via dibromo alcohols, s. J. Colonge and A. Lagier, Bl. 1949, 24, 17.)... 

Ants of different sexes and castes may produce different odoriferous compounds. Brand et al. 421), reported isolation of methyl-6-methyl-salicylate (113), 2,4-dime thy 1-2-hexenoic acid (114) and methyl anthran-ilate (115) from the mandibular glands of Camponotus noveboracensis, C. nearticus, C. rasilis and C. subbarbatus. These compounds have been found in alate females or in workers. This secretion is of crucial importance in initiating the activity of the females before swarming and is used to scent areas near the nest entrance and to induce the female to swarm from the nest when the male flight is at a maximum. 

Mycophenolic acid (6-(4 hydroxy-6-methoxy-7-methyl-3-HDxo-5- pathalanyl)-4-methyl-4-hexenoic acid) also shown to inhibit IMP dehydrogenase (9) effectively interferred with the synthesis of guanosine nucleotides from IMP by PRBC (Table 1). The decrease (85%) in labelled GTP and total guanylates was significant (p <. 001). There was also a moderate (p <. 01) decrease in the concentration of GTP and in the level of the guanylate pool. 

The other constituents arise by oxidation of the side chains and subsequent degradation. The lactone 69 (Fig. 34 peak number 37 in Fig. 33), which represents one of the most important volatile oxidation products, is not formed by oxygen oxidation of 4-methyl-2-hexenoic acid or 4-methyl-3-hexenoic acid, but is derived directly from humulone. A possible mechanism for its formation is shown in Fig. 34. 

E)- and (Z)-4-Benzyloxy-3-hydroxy-l-(4-methylphenyl)-l-butene gave, with triethyl orthoacetate in the presence of pivalic acid, the same, but enantiomeric, (R,E) and (.S , )-6-benzyloxy-3-(4-methylphenyl)-4-hexenoate [5 65%, 87% ee from the (E -butene R 78%, 90% ee from the (Z)-butene] (see p 3374)288. Similarly, (R,E)- and (S, )-6-benzyloxy-3-(4-methylphenyl)-4-hexenal are obtained by heating the (E)- and (Z)-butenes with excess methyl vinyl ether in the presence of mercury(II) acetate in a sealed tube [S 72 %, 90 % ee from the (E)-butene R 71 %, 85% ee from the (Z)-butcnc]288. Analogous strategies have been used to construct the phytyl side chain of tocopherol (see p 3370)289,290. 

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