Fig. 4.

1H NMR spectra (300 MHz) and structure of (R)-maconelliyl (S)-2-methylbutanoate.

Sex pheromone of the pink hibiscus mealybug,Maconellicoccus hirsutus, contains an unusual cyclobutanoid monoterpene

1. Aijun Zhang * , †, 
2. Divina Amalin ‡, 
3. Shyam Shirali *, 
4. Miguel S. Serrano §, 
5. Rosa A. Franqui ¶, 
6. James E. Oliver*, 
7. Jerome A. Klun *, 
8. Jeffrey R. Aldrich *, 
9. Dale E. Meyerdirk ∥, and 
10. Stephen L. Lapointe §

Author Affiliations

1. *Chemicals Affecting Insect Behavior Laboratory, Beltsville Agriculture Research Center West, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705; ‡Subtropical Horticulture Research Station, Agricultural Research Service, United States Department of Agriculture, Miami, FL 33158; §U.S. Horticultural Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Ft. Pierce, FL 34945; ¶Agricultural Experimental Station, University of Puerto Rico, Rio Piedras, PR 00928; and ∥Plant Protection and Quarantine, Animal and Plant Health Inspection Service, Agricultural Research Service, United States Department of Agriculture, Riverdale, MD 20737

http://www.pnas.org/content/101/26/9601.full

E-mail: zhanga@ba.ars.usda.gov.

Two compounds that together constitute the female sex pheromone of the pink hibiscus mealybug (PHM),Maconellicoccus hirsutus, were isolated, identified, and synthesized. They are (R)-2-isopropenyl-5-methyl-4-hexenyl (S)-2-methylbutanoate [common name is (R)-lavandulyl (S)-2-methylbutanoate] and [(R)-2,2-dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoate [which we refer to as (R)-maconelliyl (S)-2-methylbutanoate]. Maconelliol is an unusual cyclobutanoid monoterpene, and its structure has been established by enantioselective synthesis from precursors of known structure and configuration. A 1:5 synthetic mixture of the two RS esters (1 μg per rubber septum) proved to be a potent attractant of males in field bioassays. The pheromone component, maconelliyl 2-methylbutanoate, represents a heretofore undescribed natural product.

The 1H NMR spectrum (Fig. 4) of purified compound 2 (≈30 μg obtained by preparative GC) contained resonance for 26 protons, including six methyl groups, consistent with the assumed molecular formula C15H26O2. A doublet at 4.15 ppm (d, 2 H, J = 7.57 Hz) corresponded to a methylene in an ester (—O—CH2—CH—). Four distinct methyl signals were clearly displayed; two signals at 1.51 (s, 3 H) and 1.40 (s, 3 H) ppm from two methyl groups on the double bond (CH3—CC), and another two signals at 1.24 (s, 3 H) and 1.12 (s, 3 H) ppm corresponding to a geminal dimethyl [(CH3)2C—] or two methyl groups on quaternary carbons. The remaining two methyl groups supported the presence of a 2-methyl butyrate moiety CH3CH2CH(CH3)CO (δ 0.83, t, 3 H, J = 7.19 Hz; 1.077, d, 3 H, J = 6.82 Hz). Accordingly, in the absence of any olefinic protons, the tetra-substituted cyclobutane 2-methylbutanoate (compound 3 or 4, Fig. 3) were considered as reasonable pheromone candidates. The structure 3 was more consistent with the long-range homoallylic coupling (H—C—CC—CH) observed for the methylene group in the four-member ring. The two protons at the 4 position were not equivalent. Broad signals at δ 2.47 and 2.05 could be interpreted as the homoallylic long-range coupling with the terminal methyl groups on the double bond. Correspondingly, these two methyl groups (δ 1.51 and 1.40) also exhibited the same coupling pattern (coupling constant < 1 Hz). This homoallylic long-range coupling was confirmed by a 1H-1H COSY spectrum and decoupling experiments.

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[(R)-2,2-Dimethyl-3-(1-methylethylidene)-cyclobutyl]methyl (S)-2-methylbutanoate

Formula:	C15H26O2
CAS#:
MW:	238.37

Reference(s) for synthesis of [(R)-2,2-Dimethyl-3-(1-methylethylidene)-cyclobutyl]methyl (S)-2-methylbutanoate

---

Zhang, A.J., and Nie, J.Y. 2005. Enantioselective synthesis of the female sex pheromone of the pink hibiscus mealybug, Maconellicoccus hirsutus. J. Agric. Food Chem. 53:2451-2455.

Zhang, A.J., Nie, J.Y., and Khrimian, A. 2004. Chiral synthesis of maconelliol: a novel cyclobutanoid terpene alcohol from pink hibiscus mealybug, Maconellicoccus hirsutus. Tetrahedron Lett. 45:9401-9403.

nmr..............

Reference(s)

Zhang, A.J., and Nie, J.Y. 2005. J. Agric. Food Chem. 53:2451-245

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[(R)-2,2-Dimethyl-3-(1-methylethylidene)cyclobutyl]methyl (S)-2-methylbutanoate [(R)-maconelliyl (S)-2-methylbutanoate] (2a). To a solution of 2.2 mL (20.1 mmol) of (S)-(+)-2-methylbutanoic acid {Aldrich, 99% ee, [α]²⁴ _D+24.0 (c 0.1, MeOH)} in 15 mL of benzene was treated with 2.2 mL (25.2 mmol) of oxalyl chloride and 10 μl of DMF. After 1.5 h at room temperature, the benzene and excess oxalyl chloride were removed followed by the addition of another 15 mL portion of benzene. The acid chloride residue was dissolved in 15 mL of benzene, and then a solution of 1.65 g (10.7 mmol) of 6a and 18 ml (22.2 mmol) of pyridine in 15 mL of benzene were added dropwise. After stirring at room temperature for 1 h, the solvent was removed. The residue was treated with 20 mL of water, and extracted with ether. The organic solution was washed with water, 1N hydrochloric acid, 1N aqueous sodium bicarbonate, and brine, dried over sodium sulfate, and concentrated to afford yellow oil. Pure 2a (2.0 g, 79% yield) was obtained by chromatography (silica gel, 2% of ethyl acetate in hexanes). Optical purity: 99% ee; [α]²⁴ _D−0.79 (c 2.03, MeOH); ¹H NMR (C₆D₆): δ 0.84 (3H, t, J=7.19 Hz), 1.08 (3H, d, J=6.82 Hz), 1.12 (3H, s), 1.24 (3H, s), 1.36 (1H, m), 1.40 (3H, bs), 1.51 (3H, t, J=1.89 Hz), 1.67 (2H, m), 2.05 (1H, m), 2.17 (1H, m), 2.27 (1H, m), 2.48 (1H, ddt, J=14.75, 8.79, 1.52 Hz), 4.15 (2H, d, J=7.57 Hz); ¹³C NMR (C₆D₆): δ 175.76, 137.48, 122.55, 65.30, 44.43, 41.39, 39.71, 28.62, 27.79, 27.13, 21.17, 19.60, 18.64, 16.85, 11.80; EI-MS m/z (%): 238 [M]⁺ (2), 136 (29), 121 (100), 107 (12), 93 (20), 81 (26), 67 (5), 57 (16), 41 (10); HREIMS: obsd. 238.1929, calcd. for C₁₅H₂₆O₂ (M⁺): 238.1933.......http://www.google.com/patents/US8062651...









Beltsville






Beltsville Agricultural Research Center

Henry A. Wallace Beltsville Agricultural Research Center – Beltsville MD








Beltsville MD 20705-2935 & Touch Point Church Ministries Touch Point Church Ministries 11310 Montgomery Road Beltsville, Maryland 20705

(E)- 4-Oxo-2-hexenal

(E)- 4-Oxo-2-hexenal (2)

As described above for the synthesis of aldehyde 10, diol 12 (0.30 g; 2.60 mmol) was converted into compound2 (77 % yield; 0.22 g) using PCC adsorbed in Al₂O₃ (12.7 g, 10.4 mmol) and after purification through column chromatography on silica gel (hexane : ethyl ether / 1:3). IR n_max / cm^-1 2982, 1752, 1699, 1615, 1121, 980;¹H-NMR (200 MHz, CDCl₃) d 1.16 (t, J 7 Hz, 3H); 2.73 (q, J 7 Hz, 2H); 6.71-6.94 (m, 2H); 9.78 (d, J 6 Hz, 1H);¹³C-NMR (50 MHz, CDCl₃) d 7.5; 34.5; 137.2; 144.6; 193.3; 200.3; GC-MS (70 eV) m/z %: 112 (M⁺ , 16%), 97 (6%), 83 (100%), 69 (4%), 55 (77%), 39 (8% ).

Journal of the Brazilian Chemical Society

Print version ISSN 0103-5053

J. Braz. Chem. Soc. vol.11 n.4 São Paulo July/Aug. 2000

http://dx.doi.org/10.1590/S0103-50532000000400017 

Article

Alarm Pheromone System of Stink Bug Piezodorus guildinii(Heteroptera: Pentatomidae)

Paulo H. G. Zarbin^a*, Miguel Borges^b, Alcindo A. dos Santos^a, Alfredo R. M. de Oliveira^a, Fábio Simonelli^a and Francisco de A. Marques^a

^aUniversidade Federal do Paraná, Departamento de Química, CP 19081, 81531-990, Curitiba - PR, Brazil^bEmbrapa, Cenargen, Área de Controle Biológico, CP 02372, 70849-970, Brasília - DF, Brazil

http://www.scielo.br/scielo.php?pid=S0103-50532000000400017&script=sci_arttext

see

http://www.scielo.br/scielo.php?pid=S0103-50532007000600020&script=sci_arttext

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6R-(3,6-dideoxy-L-arabinohexopyranosyloxy)heptanoic acid as a pheromone compound isolated from C. elegance

 STRUCTURE

A three-dimensional stereochemistry formula (1) of 6R-(3,6-dideoxy-L-arabinohexopyranosyloxy)heptanoic acid as a pheromone compound isolated from C. elegance is determined according to spectroscopic analysis such as HR-MASS, IR, DEPT, 2D-NMR (HMBC, HMQC, NOE, ROESY, and TOCSY).

A pure molecular weight of the pheromone, 6R-(3,6-dideoxy-L-arabino-hexopyranosyloxy)heptanoic acid, is 276 dalton, and a monocular formula of the pheromone is C₁₃H₂₄O₆. A calculated high-resolution mass number of the pheromone is 276.1651. It is noted that a high-resolution mass number measured by a high resolution-FAB is 276.1652, and this mass number is almost identical to the calculated mass number (see FIG. 1). Functional groups of relative carbonyl and hydroxy groups of the pheromone molecule are identified by an infrared (IR) analysis (see FIG. 2).

In order to determine the three-dimensional stereochemistry configuration of the novel pheromone compound of formula (I), 2D-proton.nuclear magnetic resonance spectrum (¹H-NMR) is measured by using dutro-methanol (CD₃OD) as a solvent. A C-13 nuclear magnetic resonance spectrum (¹³C-NMR) is also measured by using dutro-methanol (CD₃OD) as a solvent. The chemical shift is represented by ppm.

After the location of each carbon is identified by ¹H-NMR (see FIG. 3), ¹³C-NMR (see FIG. 4) and DEPT (see FIG. 5), the chemical shift of ¹H— and ¹³C— is measured by using HMBC (see FIG. 6), HMQC (see FIG. 7), ROESY (see FIG. 8), and TOCSY (see FIG. 9) spectrums to identify the accurate relation of the ¹H— and ¹³C. Table 4 shows a result of HMBC spectrum.

In order to measure the stereo interrelation in the three-dimensional space, the two-dimensional NMR technology of NOE is used. FIGS. 10 through 12 show the obtained NOE spectrum.

The 6R-(3,6-dideoxy-L-arabino-hexopyranosyloxy)heptanoic acid of the stereochemistry formula (I) is obtained by a coupling reaction of reactants represented in formulas (II) and (III).

2,4-di-O-benzoyl-3,6-dideoxy-L-arabino-hexopyranose of formula (II) is synthesized as shown in the following reaction formula 1 from L-rhamnose monohydrate of formula (IV).

Embodiment 10 Synthesis of 6R-(3,6-dideoxy-L-arabino-hexopyranosyloxy)heptanoic acid (I)

The compound (XI) (472.9 mg, 0.976 mmol) is dissolved in MeOH (20 ml) NaOMe (52.7 mg, 0.976 mmol) is added at 0° C. The temperature is gradually increased to a room temperature and the mixture is stirred for 12 hours. After the reaction is finished, MeOH is vacuum concentrated. Then, in order to eliminate a sub-product methylbenzoate, it is dissolved in water (20 ml) and washed by CH₂Cl₂ (20 ml×5). The pH of the solution layer is adjusted using amberlite resin type acid such as amberlite and amberlite IR-120 (H⁺) (500 mg). After the filtration, the water is removed from the solution layer by freeze drying method, and then the compound (I) (234.6 mg, 87%) is isolated using flash column chromatography (EtOAc/MeOH, 11:1, v/v).

I; a colorless oil, Rf=0.43 (EtOAc/MeOH, 11:1, v/v);

[α]D²⁰=−81.0 (c=0.1, MeOH);

IR(film) Vmax 3391, 2969, 2933, 1712, 1452, 1379, 1244, 1126, 1103, 1042, 1031 cm⁻¹;

¹H NMR (500 MHz CD₃ OD) δ 4.64 (s, 1H, H-1′), 3.80-3.77 (m, 1H, H-6), 3.72-3.71 (m, 1H, H-2′), 3.63-3.59 (m, 1H, H-5′), 3.54-3.49 (m, 1H, H-4′), 2.30 (t, 2H, J=7.5 Hz; H-2), 1.96-1.92 (m, 1H, H-3′ eq), 1.79-1.74 (m, 1H, H-3′ax), 1.61 (m, 2H, H-3), 1.56-1.50 (m, 2H, H-5), 1.47 (m, 2H, H-4), 1.21 (d, 3H, J=6.5 Hz H-6′), 1.12 (d, 3H, J=6.5 Hz H-7);

¹³C NMR (125.7 MHz; CD₃OD) δ 177.7 (C-1), 97.6 (C-1′, α), 72.4 (C-6), 71.3 (C-5′), 70.1 (C-2′), 68.5 (C-4′), 38.2 (C-5), 36.1 (C-3′), 35.0 (C-2), 26.5 (C-3), 26.1 (C-4), 19.4 (C-7), 18.2 (C-6′);

An HRMS (FAB) calculated value for C₁₃H₂₅O₆) (M₊+H) m/z is 277.1651, and an actual measured value is 277.1652.

TABLE 4
(Spectrum analysis result of pheromone, 6R-(3.6-dideoxy-L- arabino-hexopyranosyloxy)
heptanoic acid
Position	δH (mult, J )	δC	HMBC (H to C)
1		177.3	2, 3
2	2.30 (t, 7.5)	34.6	1, 3
3	1.64 (m)	25.5	2, 4, 5, 6
4	1.47 (m)	25.1	2, 3, 5
5	1.50-1.48 (m)	37.1	3, 4, 6, 7
6	3.80-3.77 (m)	71.3	5, 7, 1′
7	1.14 (d, 6.5)	18.3	5, 6
1′	4.66 (s)	96.6	2′, 3′, 6
2′	3.73-3.72 (m)	69.0	1′, 3′
3′	1.97-1.95 (m)	34.9	1′, 4′, 5′
	1.79-1.74 (m)
4′	3.54-3.59 (m)	67.4	3′, 5′, 6′
5′	3.64-3.62 (m)	70.2	3′, 4′, 6′
6′	1.24 (d, 6.5)	17.2	4′, 5′

INDUSTRIAL APPLICABILITY

As described above, the present invention firstly determined stereochemistry configuration of pheromone, (6R)-6-(3.6-dideoxy-L-arabino-hexopyranosyloxy) heptanoic acid and salts thereof. Based on this fact, the effective total synthesis was successfully performed, thereby overcoming the minute isolation of the pheromone obtained from C. elegance to make it possible to mass-produce the pheromone.

Accordingly, it becomes possible to develop medical substances using the pheromone relating to aging, stress, metabolism, signal transfer system in vivo, and anti-cancer, obesity and a suppressing agent for aging and stress. In addition, it becomes also possible to research the active target protein body of the pheromone.

6R-(3,6-dideoxy-L-arabino-hexopyranosyloxy)heptanoic acid, preparation process for the same and dauer effect thereof
US 7951839 B2

http://www.google.com/patents/US7951839


DESCRIPTION OF DRAWINGS

FIG. 1 is a HR-MS-FMB spectrum of a pheromone of stereochemistry formula (1) according to the present invention;

FIG. 2 is an IR spectrum of the pheromone according to the present invention;

FIG. 3 is a ¹H-NMR spectrum of the pheromone according to the present invention;

FIG. 4 is a ¹³C-NMR spectrum of the pheromone according to the present invention;

FIG. 5 is a ¹³C-NMR DEPT spectrum of the pheromone according to the present invention;

FIG. 6 is a 2D-NMR HMBC spectrum of the pheromone according to the present invention;

FIG. 7 is a 2D-NMR HMQC spectrum of the pheromone according to the present invention;

FIG. 8 is a 2D-NMR ROESY spectrum of the pheromone according to the present invention;

FIG. 9 is a 2D-NMR TOCSY spectrum of the pheromone according to the present invention;

FIG. 10 is a 2D-NMR NOE(1) spectrum of the pheromone according to the present invention;

FIG. 11 is a 2D-NMR NOE(2) spectrum of the pheromone according to the present invention; and

FIG. 12 is a 2D-NMR NOE(3) spectrum of the pheromone according to the present invention.

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