(I) Experimental Details for Syntheses of 6,11-Hexadecadien-1-Oland the Derivatives

Supplements

General procesdures Tetrahydrofuran (THF)was distilled with CaH2 andLiAlH4, and stored under sodium threadlet. Each crude productwas dried over anhydrous Na2SO4, concentrated by rotaryevaporation under reduced pressure, and purified by columnchromatography with silica gel (SiO2, 63-210μm; Kanto Chemical Co., Japan).

(I) Experimental details for syntheses of 6,11-hexadecadien-1-oland the derivatives

(A) Synthesis of (6E,11E)- and (6Z,11E)-isomers(See Fig. 1a)

THP ether of5-bromopentan-1-ol (2) A mixture of 1,5-pentanediol (1, 5.2g, 50 mmol), HCl (0.2M, 5.0 ml), and 3,4-dihydro-2H-pyrane (DHP 15 ml) in toluene(100 ml) was stirred at room temperature (r.t.) for 3 h. The reaction mixture was poured into a saturated aqueoussolution of NaHCO3 (100 ml), the crude products were extracted with hexane (100 ml ×3), dried and concentrated, the residue was chromatographed over SiO2 (200 g) to give a mono-THP ether of 1(6.4 g). Triphenylphosphine (PPh3, 13.2 g, 50 mmol) in CH2Cl2 (10 ml) was added to the mono-THP ether (6.4 g, 34 mmol) and CBr4 (13 g, 40 mmol) in CH2Cl2 (30 ml) at 0oC. The solution was stirred at 0oC for 30 min andatr.t.overnight, thenpoured into a saturated aqueous solution of NaHCO3 (30 ml). The product was extractedwith hexane (50 ml×3),dried and concentrated, the crude product was chromatographed over SiO2 (80 g) to give2 (3.9 g, 16 mmol,31% yield from 1). 1H NMR δ: 1.51–2.0 (12H, m), 3.41 (2H, t, CH2Br, J = 7.0 Hz), 3.38 and 3.73 (2H, dt,J = 9.6, 6.7 Hz CH2OTHP), 3.50 and 3.87 (2H, m, CH2O in THP),4.57 (1H, t, J = 3.0 Hz, OCHO). 13C NMR δ: 19.7, 25.0, 25.5, 28.9, 30.8, 32.7, 33.6, 62.3, 67.2, 98.8.

THP ether of 6-pentyn-1-ol (3) The bromide 2 (3.3 g, 13 mmol) in dry DMSO (5.0 ml)was added to lithium acetylide ethylenediamine complex (1.8 g, 20 mmol) in DMSO (20 ml) at 0oC under Ar gas, and then stirred overnight. The product was extractedwith hexane (50 ml×3), washed with H2O (10 ml×2), saturated NaHCO3 (10 ml×2) and brine (10 ml×2), dried, concentratedand chromatographed over SiO2 (80 g) to give3 (2.1 g, 10.7 mmol, 81 % yield). 1H NMR δ: 1.51–1.85 (12H, m), 1.94 (1H, t, J = 2.6 Hz, C≡CH), 2.20 (2H, m, CH2C≡CH), 3.39 and 3.75(2H, dt,J = 9.6, 6.7 Hz CH2OTHP), 3.50 and 3.87 (2H, m, CH2O in THP),4.58 (1H, t, J = 3.5Hz, OCH). 13C NMR δ: 18.4, 19.7, 25.4, 25.5, 28.3, 29.2, 30.8, 62.4, 67.4, 68.2, 84.5, 98.9.

1-Iodo-(E)-4-nonene (5) Dihydropyran4 (2.2 ml, 24 mmol) was added dropwise to a stirred butyllithium (BuLi, 2.7M in hexane, 17 ml, 46 mmol) at room temperature under Ar. The mixture was heated under reflux for 3 h and then cooled. An excess of BuLi was destroyed by the slow addition of water, with cooling. The crude product was extracted with ether, dried, concentrated andchromatographed over SiO2 (20 g) to give5(1.4 g, 17mmol, 70% yield). Iodine (2.4 g, 9.4 mmol) was added to a solution of triphenylphosphane (4.2 g, 16 mmol) and imidazole (1.1 g, 16 mmol) in dry ether (80 ml) at 0 °C under Ar. After stirring for15 min, (E)-4-nonene-1-ol (1.2 g, 8.5 mmol) dissolved in dry ether (5 mL) wasadded by using a syringe. The mixture was stirred at r.t. for 2 h, the precipitates were filtered. The eluent was poured into water, and the crude product was extracted with hexane,washed with an aqueous solution of Na2S2O3,dried, concentrated, and chromatographed over SiO2 (20 g) to give 5 (1.8 g, 7.2mmol,84% yield) 1H NMR δ:0.89 (3H, t, J = 7.0 Hz, CH3), 1.32 (4H, m, CH3CH2CH2), 1.87 (2H, m, CH2CH2I), 2.04 (4H, m, CH2CH=CHCH2), 3.18 (2H, t, J = 6.9 Hz, CH2I), 5.40 (2H, m, CH=CH). 13C NMR δ: 6.7, 14.0, 22.2, 31.7, 32.3, 33.1 (×2), 127.7, 132.3.

THP ether of (E)-11-hexadecen-6-yn-1-ol (6) BuLi (1.6min hexane, 1.2 ml, 1.9 mmol) was added dropwise to a mixture of 3 (370mg, 1.9 mmol), hexamethylphosphoramide (HMPA, 4.0 ml), and THF (20 ml) stirred at -35oC under Ar. The mixture was stirred at -20oC for 1h, and5 (400mg, 1.6 mmol) dissolved in THF (2.0 ml) was added dropwise. After stirringat r.t. overnight,the reactionmixture was quenched with water (5.0 ml). The crude product was extracted with hexane (20 ml×3), washed with a saturated aqueous solution of NH4Cl (10 ml×2) and brine (10 ml×2), dried, concentrated andchromatographed over SiO2 (20 g) togive6 (440 mg, 1.4mmol,71% yield). 1H NMR δ:0.89 (3H, t, J = 6.9 Hz, CH3), 1.32 (4H, m), 1.45–1.80 (14H, m), 1.98 (4H, m, CH2CH=CHCH2), 2.14 (4H, m, CH2C≡CCH2), 3.39 and 3.74(2H, dt,J = 9.6, 6.7 Hz CH2OTHP), 3.50 and 3.87 (2H, m, CH2O in THP), 4.58 (1H, t, J = 3.5 Hz, OCH), 5.39 (2H, m, CH=CH). 13C NMR δ: 14.0, 18.2, 18.7, 19.7, 22.2, 25.5, 29.0, 29.1 (×2), 29.3, 30.7, 31.7, 31.8, 32.3, 62.3, 67.5, 80.1, 80.2, 98.8, 129.2, 131.2.

(6E,11E)-6,11-Hexadecadien-1-ol (E6,E11-16:OH) The enyne compound 6 (220mg, 0.68 mmol) andp-TsOH (110mg) dissolved inCH3OH (10 ml) was stirred for 2h at r.t. The mixture was poured into a saturated aqueous solution ofNaHCO3(10 ml),the product was extracted with hexane (10 ml×3),washed withbrine (10 ml×2), dried, concentrated andchromatographed over SiO2 (3.0 g) to give(E)-11-hexadecen-6-yn-1-ol (170mg, 0.58 mmol, 85% yield). Next, LiAlH4 (90mg, 2.4 mmol) was added in portions to an ice-cooled mixture of dry diglyme (3.0 ml) and THF (0.2 ml) under Ar. After foaming subsided, the(E)-11-hexadecen-6-yn-1-ol(130mg, 0.47 mmol)dissolved in dry diglyme (1.0 ml) was added to the suspension of LiAlH4 and stirred for 10 min. Furthermore, the mixture was stirred for 20 h at 140oC, and then cooled to 0oC. After adding hexane (8.0 ml), the mixture was sequentially treated with water (0.2 ml), a NaOH solution (20%, 0.16 ml), and water (0.75 ml)in a cautious dropwise manner, and was stirred for 30 min to allow precipitate to white gummy slurry. The hexane layer was recovered and the residue was rinsed with hexane(15 ml×3). The hexane extract was washed with water(10 ml×2) and brine(10 ml×2), dried, concentrated and the crude product was chromatographed over SiO2 (5 g) to giveE6,E11-16:OH (69 mg, 0.27 mmol, 58% yield).

(6Z,11E)-6,11-Hexadecadien-1-ol(Z6,E11-16:OH) Nickel acetate tetrahydrate(200mg, 0.80 mmol) was dissolved in EtOH(99.5%, 15 ml)and the solution was stirred under H2 gas. NaBH4 (120 mg, 3.2mmol) dissolved in EtOH (5.0 ml)was injected to reduce nickel acetate toa P-2 Ni catalyst. After finish of gas evolution, the reactor wasagain purged with H2 gas, and ethylenediamine (0.25 ml)was mixed. After stirring for 10 min,6(220mg, 0.68 mmol) in EtOH (99.5%, 5.0 ml) was introduced into the reactor. Quantitative uptake of H2 gas wasfinished within2hand the absence of 6was confirmed by TLC. The catalyst was filtered and most of EtOH was evaporated. The residue was poured into water (10 ml) and the product was extracted with hexane (30 ml ×3).The hexane extract was washed with brine; dried; and concentrated. The residue was added in EtOH (10 ml)andp-TsOH (110mg, 0.63 mmol), and the mixturewas stirred for 2.5h at r.t. The mixture was poured into a saturated aqueous solution ofNaHCO3(10 ml), and the product was extracted with hexane (20 ml×3). dried, concentrated and the crude product was chromatographed over SiO2 (10 g) to giveZ6,E11-16:OH (180mg, 0.74 mmol, 93% yield).

(6E,11E)-6,11-Hexadecadienyl acetate (E6,E11-16:OAc) A mixture of E6,E11-16:OH (18 mg, 0.076 mmol), pyridine (0.1 ml), and acetic anhydride (2.0 ml) was stirred at r.t. for 1 h. Crude products were poured into a saturated NaHCO3 solution (5 ml), extracted with hexane (10 ml × 3),dried, concentrated andchromatographed over SiO2 (2 g) to give E6,E11-16:OAc (19 mg, 0.069 mmol,91% yield). 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.31-1.42 (10H, m, CH2×5), 1.61 (2H, m, CH2CH2O), 1.98 (8H, m, CH2CH=CHCH2×2), 2.04 (3H, s, CH3C=O), 4.05 (2H, t, J = 6.7 Hz, CH2OH), 5.38 (4H, m, CH=CH×2);13C NMR δ ppm:14.0, 21.0, 22.2, 25.9, 28.6, 29.0, 29.1, 31.1, 31.8, 32.1, 32.3, 32.6, 64.7, 130.1, 130.2, 130.5, 130.6, 171.3.

The (6Z,11E)-Isomer (Z6,E11-16:OAc) was synthesized from Z6,E11-16:OH in the same manner. 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.30-1.45 (10H, m, CH2×5), 1.63 (2H, m, CH2CH2O), 2.0 (8H, m, CH2CH=CHCH2×2), 2.04 (3H, s, CH3C=O), 4.05 (2H, t, J = 6.7 Hz, CH2OH), 5.37 (4H, m, CH=CH×2);13C NMR δ ppm:14.0, 21.0, 22.2, 25.9, 26.7, 27.2, 28.6, 29.2, 31.1, 31.8, 32.2, 32.3, 64.7, 129.7, 130.0 (×2),130.7, 171.3.

(6E,11E)-6,11-Hexadecadienal (E6,E11-16:Ald) E6,E11-16:OH (23 mg, 0.095 mmol) dissolved in CH2Cl2 (1.0 ml) was added dropwise to a mixture of pyridinium chlorochromate(PCC,25 mg, 0.09 mmol) in CH2Cl2 (5.0 ml).After stirring for 1 h at r.t., powdery MgSO4 (200 mg) was added and the mixture was stirred for 10 min. The solvent was decanted and the residue was washed with hexane (10 ml×3). The two organic layerswere combined and washed with brine (5 ml×2), dried, concentrated and the crude product was chromatographed over SiO2 (3.0 g) to giveE6,E11-16:Ald(19 mg, 0.082 mmol,86% yield). 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.32–1.38 (8H, m, CH=CHCH2CH2×4) 1.64 (2H, m, CH2CH2CHO), 1.98 (8H, m, CH2CH=CHCH2×2), 2.44 (2H,td, J =7.2, 1.8 Hz,, CH2CHO), 5.38 (4H, m, CH=CH×2), 9.76 (1H, t, J =1.8 Hz, CHO);13C NMR δ: 14.0, 21.5, 22.2, 29.0, 29.5, 31.8, 32.0, 32.0, 32.3, 32.3, 43.8, 129.7, 130.0, 130.6, 130.7, 203.0.

The (6Z,11E)-Isomer (Z6,E11-16:Ald) was synthesized from Z6,E11-16:OH in the same manner. 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.32–1.40 (8H, m, CH=CHCH2CH2×4) 1.63 (2H, m, CH2CH2CHO), 1.98 (8H, m, CH2CH=CHCH2×2), 2.44 (2H,td, J =7.2, 1.8 Hz, CH2CHO), 5.38 (4H, m, CH=CH×2), 9.77 (1H, t, J =1.8 Hz, CHO);13C NMR δ: 14.0, 21.7, 22.2, 26.7, 26.9, 29.2, 29.6, 31.8, 32.2, 32.3, 43.8, 129.1, 130.0, 130.3, 130.8, 202.8.

(B) Synthesis of (6E,11Z)- and (6Z,11Z)-isomers(See Fig. 1b)

(Z)-1-Iodo-4-nonene (8) NaI (5.7 g, 38 mmol)was dissolved in acetone (45 ml), 1-chloro-4-nonyne7(2.0 g, 13 mmol) was added to the solution and stirred for 4h at r.t.. 1-Iodo-4-nonynewas extracted with hexane, washed with saturated NaHCO3 solution(10 ml×2) and brine(10 ml×2), dried and concentrated. Without purification, a triple bond of the product wasreduced to a (Z)-double bond in the same manner for the preparation of Z6,E11-16:OH, and8 (2.7 g, 10.7 mmol, 85%yield) was yielded. 1H NMR δ:0.90 (3H, t, J = 7.0 Hz, CH3), 1.33 (4H, m, CH3CH2CH2), 1.88 (2H, m, CH2CH2I), 2.10 (4H, m, CH2CH=CHCH2), 3.19 (2H, t, J = 6.9 Hz, CH2I), 5.36 (2H, m, CH=CH). 13C NMR δ: 6.7, 14.0, 22.4, 27.1, 27.9, 31.9, 33.4, 127.2, 131.8.

THP ether of (Z)-11-hexadecen-6-yn-1-ol (9) In the same manner for thesynthesis of 6, iodide 8(800mg, 3.2 mmol) was coupled with alkyne3 (570mg, 2.9mmol) to give 9(770mg, 2.4 mmol, 83% yield). 1H NMR δ:0.89 (3H, t, J = 6.9 Hz, CH3), 1.32 (4H, m, CH3CH2CH2), 1.54 (6H, m, CH2CH2CH2), 1.45-1.80 (8H, m, CH2CH2CH2CH2O, CH2CHO), 1.98 (4H, m, CH2CH=CHCH2), 2.14 (4H, m, CH2C≡CCH2), 3.38 and 3.73(2H, dt,J = 9.6, 6.7 Hz CH2OTHP), 3.51 and 3.87 (2H, m, CH2O in THP), 4.58 (1H, t, J = 3.5 Hz, OCH), 5.36 (2H, m, CH=CH). 13C NMR δ: 14.0, 18.3, 18.7, 19.7, 22.4, 25.5, 26.2, 26.3, 27.0, 28.8, 29.0, 29.7, 30.8, 32.2, 62.3, 67.5, 80.1, 80.2, 98.8, 128.7, 130.8.

(6E,11Z)-6,11-Hexadecadien-1-ol, the (6Z,11Z)-isomer, and their derivatives All compounds were synthesized in the same manner for the preparation of (6E,11E)-isomers. E6,Z11-16:OAc; 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.31-1.42 (10H, m, CH2×5), 1.61 (2H, m, CH2CH2O), 1.98 (8H, m, CH2CH=CHCH2×2), 2.04 (3H, s, CH3C=O), 4.05 (2H, t, J = 6.7 Hz, CH2OH), 5.38 (4H, m, CH=CH×2);13C NMR δ ppm:14.0, 21.0, 22.4, 25.9, 26.7, 28.6, 29.0, 29.5, 32.0, 32.1, 32.2, 32.3, 64.7, 129.6, 130.1, 130.2, 130.6, 171.3. Z6,Z11-16:OAc; 1H NMR δ ppm: 0.89 (3H, t, J =7.0 Hz, CH3), 1.31-1.42 (10H, m, CH2×5), 1.62 (2H, m, CH2CH2O), 2.03 (8H, m, CH2CH=CHCH2×2), 2.04 (3H, s, CH3C=O), 4.05 (2H, t, J = 6.7 Hz, CH2OH), 5.36 (4H, m, CH=CH×2);13C NMR δ ppm:14.0, 21.0, 22.4, 25.9, 26.9 (×3), 27.2, 28.6, 29.2 (×2), 32.0, 64.7, 129.5, 129.7, 130.1, 130.2, 171.3. E6,Z11-16:Ald; 1H NMR δ ppm: 0.90 (3H, t, J =7.0 Hz, CH3), 1.32–1.40 (8H, m, CH=CHCH2CH2×4) 1.64 (2H, m, CH2CH2CHO), 2.01 (8H, m, CH2CH=CHCH2×2), 2.44 (2H,td, J =7.2, 1.8 Hz, CH2CHO), 5.38 (4H, m, CH=CH×2), 9.76 (1H, t, J =1.8 Hz, CHO);13C NMR δ: 14.0, 21.5, 22.4, 26.7, 26.9, 29.0, 29.6, 31.9, 32.1, 32.3, 43.8, 129.5, 129.7, 130.2, 130.8, 202.9. Z6,Z11-16:Ald; 1H NMR δ ppm: 0.90 (3H, t, J =7.0 Hz, CH3), 1.32–1.42 (8H, m, CH=CHCH2CH2×4) 1.65 (2H, m, CH2CH2CHO), 2.03 (8H, m, CH2CH=CHCH2×2), 2.43 (2H,td, J =7.2, 1.8 Hz, CH2CHO), 5.36 (4H, m,CH=CH×2), 9.77 (1H, t, J =1.8 Hz, CHO);13C NMR δ: 14.0, 21.7, 22.3, 26.8, 26.9 (×3), 29.2, 29.8, 31.9, 43.8, 129.2, 129.4, 130.3 (×2), 202.8.

(II) Experimental details for syntheses of 4,9-tetradecadien-1-oland the derivatives (See Fig. 2)

THP ether of 4-pentyn-1-ol(11) DHP (3.4 g, 40 mmol) dissolved in CH2Cl2 (20 ml)was added dropwise to 4-pentyn-1-ol (10, 3.0 g, 36 mmol) andp-TsOH(80mg, 0.46 mmol)dissolved inCH2Cl2 (40 ml). The reaction mixture was stirred for 2.5 hat r.t.,and was poured into a saturated aqueous solution of NaHCO3 (50 ml). The product was extractedwith hexane (60 ml×3),dried, concentrated and the crude product was chromatographed over SiO2 (60 g) to give11 (5.8 g, 35mmol, 97% yield). 1H NMR δ: 1.51–1.85 (8H, m), 1.95 (1H, t, J = 2.6 Hz, C≡CH), 2.31 (2H, m, CH2C≡CH), 3.47 and 3.82 (4H, m, CH2OTHP and CH2O in THP), 4.59 (1H, t, J = 3.4Hz, OCHCH2). 13C NMR δ: 15.3, 19.5, 25.5, 28.7, 30.7, 62.2, 65.8, 68.5, 84.0, 98.8.

THP ether of (E)-9-Tetradecen-4-yn-1-ol (12) BuLi (1.6min hexane, 1.2 ml, 1.92 mmol) was added dropwise to a stirred mixture of 11 (320mg, 1.9 mmol), hexamethylphosphoramide (HMPA, 0.4 ml), and THF (20 ml) at -35oC under Ar. The mixture was warmed to -20oC and stirred for 1h. Next,iodide 5 (400mg, 1.6 mmol) dissolved in THF (2.0 ml) was added dropwise, the reaction mixture was warmed to r.t. After overnight stirring,the reactionmixture was quenched with water (5.0 ml). The product was extracted with hexane (20 ml×3) and washed with a saturated aqueous solution of NH4Cl (10 ml×2) and brine (10 ml×2), dried, concentrated andchromatographed over SiO2 (20 g) togive12 (460 mg, 1.6mmol,83% yield). 1H NMR δ:0.89 (3H, t, J = 6.9 Hz, CH3), 1.32 (4H, m, CH3CH2CH2), 1.54 (6H, m, CH2CH2CH2), 1.77 (4H, m, CH2CH2O, CH2CHO), 2.02 (4H, m, CH2CH=CHCH2), 2.20 (4H, m, CH2C≡CCH2), 3.49 and 3.82 (4H, m, 4H, m,CH2OTHP and CH2O in THP), 4.6 (1H, t, J = 3.4 Hz,CH2OCH), 5.39 (2H, m, CH=CH). 13C NMR δ: 14.0, 15.6, 18.1, 19.5, 22.2, 25.5, 29.0, 29.3, 30.7, 31.7, 31.8, 32.3, 62.1, 66.1, 79.6, 80.4, 98.8, 129.2, 131.3.

THP ether of (Z)-9-Tetradecen-4-yn-1-ol (13) In the same manner for thesynthesis of 12, iodide 8(0.8 g, 3.2 mmol) was coupled with alkyne 11 (490 mg, 2.9mmol) to give 13(670mg, 2.3 mmol, 80% yield). 1H NMR δ:0.89 (3H, t, J = 6.9 Hz, CH3), 1.32 (4H, m, CH3CH2CH2), 1.54 (6H, m, CH2CH2CH2), 1.77 (4H, m, CH2CH2O, CH2CHO), 2.02 (4H, m, CH2CH=CHCH2), 2.20 (4H, m, CH2C≡CCH2), 3.49 and 3.82 (4H, m, 4H, m, CH2OTHP and CH2O in THP), 4.58 (1H, t, J = 3.4 Hz,CH2OCH), 5.35 (2H, m, CH=CH). 13C NMR δ: 14.0, 15.7, 18.1, 19.5, 22.3, 25.5, 26.3, 27.0, 29.0, 29.7, 30.7, 32.0, 62.1, 66.1, 79.6, 80.4, 98.8, 128.6, 130.7.

4,9-tetradecadien-1-oland its derivatives From 12 and 13, all four geometrical isomers of 4,9-tetradecadien-1-oland its derivatives were synthesized in the same manner for the corresponding6,11-dienyl compounds. NMR data are shown in supplemental Tables S1 and S2.

1