2-Heptanone, 6-hydroxy-6-methyl

Novotny M., Jemiolo B., Wiesle D., Ma W., et al. (1999). A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice. Chem Biol 6, 377-383. 

Deleting a cluster of 16 Vlr genes (2 of the 12 Vlr gene families representing about 12% of the Vlr repertoire) impairs sexual and maternal behavior. Gene-deficient male mice initiate fewer sexual encounters, and lactating females attack intruders less. Furthermore, both mutant male and female mice showed specific anosmia in that VNO did not respond to three of eight tested pheromonal compounds (6-hydroxy-6-methyl-3-heptanone, n-pentyl acetate, and isobutylamine) (Del Punta etal., 2002). 

Dimethyl-2-ethyltetrahydrofuran-2-ol 6-Hydroxy-6-methyl-3-heptanone FIGURE 8.2 The active compounds in the urine of dominant male mice. 

Another unique mouse urinary constituent is 6-hydroxy-6-methyl-3-heptanone, existing in aqueous solutions in equilibrium with its cyclic tautomer, 5,5-dimethyl-2-... 

Although we had observed these dehydration analysis artifacts during our early GC/MS runs (Harvey, Wiesler Novotny, 1989), we could not find a clear-cut biological activity for them (unpublished experiments). In contrast, 6-hydroxy-6-methyl-3-heptanone showed a significant biological activity in the uterine assays (Novotny, Jemiolo, et al., 1998). 

Based on our recent investigations, the following scenario (Novotny, Ma, et al., 1998) concerning male primer pheromones appears plausible (1) under the control of testosterone, normal males produce the more lipophilic famesenes to be excreted into the urine via the preputial gland, while the more polar SBT, DHB and 6-hydroxy-6-methyl-3-heptanone are contained in the bladder urine (2) all pheromones that have now been implicated in estms induction and puberty acceleration are volatile ligands that bind... 

Halide exchange reaction, 66, 87 2,5-Heptadien-4-ol, 3,4,5-trimethyl-, 65, 42 Heptanal (111-71-7), 65, 26 3-HEPTANONE, 4-METHYL-, (S)-, 65, 183 5-Heptynoic acid, 7-hydroxy-, methyl ester, 67, 193... 

Very recently (R, S )-4-methyl-5-hydroxy-3-heptanone has been identified as the major component of the aggregation pheromone of the rice weevil, sltophilus orvzae L., and the maize weevil, S. zeamals Motsch. (28). This compound is obviously very different in structure from the previously identified curculionid pheromones. In fact, it is very similar to the pheromone of two other stored-products pests, the drugstore beetle and the cigarette beetle, which are in the family Anobiidae (see later). Undoubtedly, we will find more diversity in structure as more curculionid pheromones are identified. 

CeHi2 O2, 4-Hydroxy-4-methyl-2-pentanone, CH3C(0)CH2C(0H)(CH3)CH3 OH, 696 AF, 698 CS, 1180 J, 1180 C7H14O2, 5-Hydroxy-2-heptanone, CH3C(0)CH2CH2CH0H)CH2CH3 OH, 697 AF, 698... 

R — (CH,),C6H5 (4SJR)-5-hydroxy-4-methyl-5-phenyI-3-heptanone yield 55%... 

Hydroxy-4-methyl-7-phcnyl-3-heptanone 10, R1 = (CH2)2C6H5 Typical Hydrolysis Procedure5 ... 

Two propanoate units (see Fig. 2) seem to be coupled in 1-ethylpropyl (2S,3.R)-2-methyl-3-hydroxypropanoate 221, the male produced aggregation pheromone of the granary weevil, Sitophilus granarius [390-393]. Even the ester-moiety may origin from two propanoate units after decarboxylation and reduction Three propanoate units (and decarboxylation, see Fig. 2) may produce (4S,5 )-5-hydroxy-4-methyl-3-heptanone, sitophilure 222, the aggregation pheromone of the rice weevil, Sitophilus oryzae [394, 395]. The same carbon skeleton is present in the achiral 4-methylheptan-3,5-dione 223, the pheromone of the pea weevil, Sitona lineatus [396-398]. 

Bohman B, Unelius CR (2009) Synthesis of all four stereoisomers of 5-hydroxy-4-methyl-3-heptanone using plants and oyster mushrooms. Tetrahedron 65 8697-8701... 

Hexanone, 2-heptanone, 2-octanone, 2-nonanone, 6-methyl-5-hepten-2-one, fenchone, carvone, acetophenone, 2-hydroxy-4,6-dimethoxy-5-methylacetophenone... 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

The way to the 15-hydroxyderivatives was opened by N-alkylation of 225 with l-bromo-2-heptanone in ethanol to 229a in good yield. The reaction product 229a (free base m.p. 131 °C/hydrochloride m.p. 77 °C) was then used for the preparation of the 15-methyl-15-hydroxy and the 15-hydroxyderivatives. 

Conversion of enantiomerically pure ethyl (R)-3-hydroxybutanoate to (55,6/ )-B and lSR,6R)-W, the other building blocks, is summarized in Figure 4.56. The crucial step was the chromatographic separation of a mixture of (5S,6R)- and (5Z ,6/ )-6-hydroxy-5-methyl-2-heptanone. This could be achieved, because the former was less polar due to the facile hemiacetal formation. The hemiacetal was crystalline. 

Sitophilus oryzae Sitophinone 5-hydroxy-4-methyl-3-heptanone... 

Methyl-5-hepten-2-one in 35% sulfuric acid adds water at room temperature, forming 6-hydroxy-6-methyl-2-heptanone 67... 

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