氨基酸的合成

1、Stereoselective Synthesis of Amino acid and its derivant 目 录1. 前言22 U.Schollkopf法-从氨基酸模块开始的合成2.1 U.Schollkopf法-从氨基酸模块开始的合成示例2.2 3.2 Synthesis of the key intermediate of the novel rennin inhibitor Aliskiren2.3 Efficient syntheses of biologically important amino acidSynthesis of -amino acid and its de

2、rivant from aziridine3 synthesis of the amino acids from 2-isopropyl-3,6-dimethoxy (or: diethoxy)-2,5-dihydro-pyrazine4 4. Synthesis of -amino acid from Evans Reagent1前言不对称合成a-氨基酸的工作自1970年代后期系统地开展起来，在其后的十余年中，发现了几十种不对称合成方法。已经报道的a-氨基酸不对称合成方法可以分为五类，即酶合成法、-脱氢氨基酸氢化或环加成法、Strecker型反应、亲电或亲核氨基化法以及亲电或亲核烷基化法，上

3、述反应都涉及-碳的手性控制.就立体选择性的控制方法而言，手性辅基(chiral auxiliary)方法仍占多数。用于 不 对 称合成a-氨基酸的手性辅基种类较多，常见的环系模板(cyclic templates)(也叫环系手性辅基)和非环系模板(acyclic templates)（也叫非环系手性辅基）应用 手 性 辅基的a-氨基酸不对称合成方法甘氨酸或丙氨酸衍生烯醇盐(enolates)的亲电烷基化是最早发展的a-氨基酸合成方法，该法变化形式丰富，研究和应用广泛，其中有几种已成为当前制备手性氨基酸的常规方法. U.Schollkopf法从氨基酸模块开始的合成, D.Seebach法-手性中

4、心自我再生”原理的成功应用, Y. N. Belokon法含甘氨酸席夫碱的金属配位化合物, W.Oppolzer法-方便回收的天然手性源辅基, D.A .E vans法-一种广泛应用的手性辅基, M.J .O Donnell法-基于金鸡纳碱的手性相转移催化。2.制备手性氨基酸的常用方法 21 U.Schollkopf法-从氨基酸模块开始的合成U.Schollkopf用L-Val和Gly缩合制得环二肽7,7与Meerwein盐(Me30+BF4-)作用得甲基醚1，经丁基锂脱质子得甘氨酸负离子8，烷基化生成9，酸水解，得手性a-氨基酸10. 此法所得氨基酸的ee值可达95%以上. 制备反应如Sch

5、eme 1所示。 Scheme1Example:2.1.1 U.Schollkopf法-从氨基酸模块开始的合成示例References: Tetrahedran Asymmetry, 10 (1999), 41514156.To a stirred suspension of D-valine 1 (117.15 g, 1.0 mol) in THF (1200 mL) was added phosgene (148.5 g, 0.5 mol), the temperature was maintained at 40 with a heating mantle. After the soli

6、d in solution disappeared, the solution which resulted was purged with N2 for 2 h, the solvent was removed in vacuo and the residue was flashed with THF twice, the N-carboxyanhydride which formed was dried in the vacuum to provide a rude product 2 (206.37 g, 100%), due to the unstable nature of this

7、 anhydride it was used immediately in the next step without further purification.A solution of the N-carboxyanhydride 2 (206.37 g, 1.44 mol) in THF (1600 mL) was added dropwise to a vigorously stirred mixture of glycine ethyl ester hydrochloride 3 (201.32 g, 1.44 mol), triethylamine (461 mL, 3.31 mo

8、l), and chloroform (2000 mL ) at 70 . After 3 h of stirring at 70 and 2 h at room temperature, the reaction solution was filtered to remove the triethylamine hydrochloride, the filtrate was concentrate in vacuo to give the residue 4. The residue 4 was added toluene, the suspension which resulted was

9、 heated at reflux for 12 h and then cooled to 0 , the bis-lactim which resulted was recovered by vacuum filtration, washed with ether and dried under vacuum at 100 to provide the pure compound 5.To a stirred solution of triethyloxonium tetrafluoroborate 6 (1063.19 g, 5.60 mol) in CH2Cl2 was added th

10、e bislactim 5 (291 g, 1.86 mol) in portions, after several hours the reaction mixture became homogeneous, the reaction was stirred at room temperature under N2 for 3 days, after which a solution of NaH2PO4 and Na2HPO4 in water was added to the solution with stirring, the organic phase was separated

11、and the aqueous phase was re-extracted with CH2Cl2 twice. The combined organic layers were dried over MgSO4, evaporated to remove the solvent, the residue was vacuum distilled to provide the pure bis-ethoxy lactim ether 7.n-BuLi (1.6 M in hexanes, 9.6 mL, 15.4 mmol) was added to a 78C solution of (R

12、)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine 7 (3, 2.5 mL, 14 mmol) and 1,3-dimethyl-2-imidazolidinone (DMEU,3.1 mL, 28 mmol) in dry THF (140 mL). After 45 min, a solution of 2-bromoethyl triphenylmethylsulfide 8 (6.32 g, 16.5 mmol, 1.2 equiv.) in dry THF (30 mL) was added over 25 min. After 20 h

13、 at 78C, the cherry colored reaction mixture was quenched with 5 mL of 100 mmol, pH 7.2 phosphate buffer and warmed to ambient temperature. The yellow solution was concentrated in vacuo and the resulting residue was partitioned between ethyl acetate (EtOAc, 100 mL) and water (100 mL). The aqueous la

14、yer was separated and extracted with EtOAc (50 mL). Combined organic extracts were dried over Na2SO4, decanted and concentrated in vacuo to give an oil. Purification by flash chromatography (5% EtOAc/hexanes) gave 1.60 g (47% based on recovered starting material) of (2R,5S)-2-isopropyl-3,6-dimethoxy

15、-5-2-(tritylsulfanyl)ethyl-2,5-dihydropyrazine 9. Compound 9: 1H NMR (CDCl3) _ 7.427.38 (m, 5H), 7.297.12 (m, 10H), 3.96 (ddd, J=7.2, 3.6, 3.6Hz, 1H), 3.81 (dd, J=3.6, 3.6 Hz, 1H), 3.61 (s, 3H), 3.55 (s, 3H), 2.272.07 (m, 2H), 1.991.88 (m, 1H), 1.781.66 (m, 1H), 1.00 (d, J=6.6 Hz, 3H), 0.65 (d, J=6.

16、9 Hz, 3H); 13C NMR (CDCl3) _ 163.67, 163.22, 144.98, 129.60, 127.75, 126.47, 66.51, 60.73, 54.52, 52.36, 33.19, 31.78, 27.75, 18.99, 16.64; ESMS (M+2H)2+ 243.2. Analytical HPLC (2% EtOAc/hexanes): Rt=7.72 minA 0.50 M aqueous solution of hydrochloric acid (10.1 mL, 5.06 mmol, 2.1 equiv.) was added to

17、 a solution of (2R,5S)-2-isopropyl-3,6-dimethoxy-5-2-(tritylsulfanyl)ethyl-2,5- dihydropyrazine (1.17 g, 2.41 mmol) in dioxane (10.1 mL) and stirred for 6 h at ambient temperature. The solution was then adjusted to pH 10 with concentrated ammonium hydroxide and extracted with CHCl3 (340 mL). Combine

18、d organic extracts were dried (Na2SO4), decanted and concentrated in vacuo. The residual oil was purified by flash column chromatography (5% MeOH/CH2Cl2; Rf=0.37) to afford methyl (2S)-2-amino-4- (tritylsulfanyl)butanoate 5 as a thick colorless oil (840 mg, 89%). 1H NMR (CDCl3) 7.437.39 (m, 5H), 7.3

19、17.18 (m, 10H), 3.64 (s, 3H), 3.433.38 (m, 1H), 2.30 (t, J=7.8 Hz, 2H), 1.801.70 (m, 1H), 1.581.46 (m, 1H); 13C NMR (CDCl3) 175.85, 144.79, 129.59, 127.86, 126.62, 66.77, 53.48, 51.96, 33.95, 28.31The Mosher amide of 10 was prepared by adding triethylamine (10.2 mL, 0.073 mmol) and (R)-()-(-)-methox

20、y-(trifluoromethyl)phenylacetic acid chloride (13.6 mL, 0.073 mmol) in successionto a solution of methyl (2S)-2-amino-4-(tritylsulfanyl)butanoate (5, 19 mg, 0.05 mmol) in anhydrousdichloromethane (1 mL) and stirred for 3 h at ambient temperature then quenched by addition of water (100 mL). After 15

21、min of stirring, dichloromethane (20 mL) was added and washed with water (20 mL).The organic layer was separated, dried (Na2SO4), decanted and concentrated in vacuo to afford an oilwhich was purified by flash chromatography to afford 22 mg (72%) of the Mosher amide of 10. 1H NMR (CDCl3) 7.517.42 (m,

22、 2H) 7.357.15 (m, 18H), 6.93 (d, J=8.4 Hz, 1H), 4.554.48 (m, 1H), 3.66 (s,3H), 3.47 (d, J=1.5 Hz, 3H), 2.252.15 (m, 1H), 2.091.98 (m, 1H), 1.831.71 (m, 1H), 1.541.38 (m,1H); 19F NMR (CDCl3) : 6.15.A 0.50 M LiOH solution (9.0 mL, 4.5 mmol, 2.02 equiv.) was added dropwise to a solution of ester 10 (77

23、2 mg, 1.98 mmol) in dioxane (9.0 mL) and stirred at room temperature for 3 h. The reaction mixturewas concentrated in vacuo and the residual solid was suspended in water (20 mL). Careful adjustmentto pH 8 with 1 M aqueous HCl afforded a precipitate. The white solid thus obtained was filtered anddrie

24、d under high vacuum at 46C over P2O5 to give (2S)-2-amino-4-(tritylsulfanyl) butanoic acid 11 (, Striphenylmethyl-L-homocysteine, 687 mg, 92%). 1H NMR (DMSO-d6): 7.487.18 (m, 15H), 3.02 (t, J=6.3 Hz, 1H), 2.26 (t, J=5.1 Hz, 2H), 1.901.73 (m, 1H), 1.691.53 (m, 1H); 13C NMR (DMSO-d6): 169.17, 144.51,

25、129.05, 127.93, 126.62, 65.90, 53.43, 30.40, 28.11;Sodium metal (61 mg, 2.65 mmol) was added to a suspension of S-triphenylmethyl-L- homocysteine (11, 270 mg, 0.72 mmol) in 20 mL of liquid ammonia at 33. After 1 h, the reaction mixture was warmedto ambient temperature and concentrated in vacuo. (Cau

26、tion: the product is extremely air sensitive.Exposure to air should be kept to a minimum.) The resulting solid was suspended in deaerated water (10 mL) and extracted with deaerated ether (10 mL) to remove triphenylmethane. The aqueous layer was adjusted to pH 6 by careful addition of deaerated 47% a

27、queous HI. This solution was concentrated invacuo and any remaining HI was removed by azeotroping with deaerated water (3*10 mL). The residue was stirred in deaerated hot ethanol for 15 min, cooled to ambient temperature under nitrogen and filtered. The filtered solid was isolated and dried under hi

28、gh vacuum for 15 h at 56 to afford 51 mg (52%) of L-homocysteine 14. 1H NMR (D2O): 3.73 (dd, J=7.4, 5.7 Hz, 1H), 2.602.42 (m, 2H), 2.121.88 (m, 2H); 13C NMR (D2O): 174.61, 53.97, 34.98, 20.15; Sodium metal (141 mg, 6.13 mmol) was added to a suspension of 11 (200 mg, 0.53 mmol) in 40 mL of liquid amm

29、onia at 33C and stirred for 3.5 h. Unreacted sodium metal was quenched by the addition of a few crystals of NH4Cl. Ammonia was allowed to evaporate by warming to ambient temperature and any residual ammonia was removed in vacuo. Deaerated water (50 mL) was poured into the flask and the mixture was e

30、xtracted with deaerated ether (2* 25 mL). The aqueous layer was adjusted to pH 7 by the careful addition of deaerated concentrated HCl, the mixture treated with decolorizing carbon, filtered through Celite and the filter pad washed with deaerated water (15 mL). The resulting filtrate was flushed wit

31、h air for 1 h and left sitting open to air for 12 h. Filtration removed trace suspended solids and the filtrate was concentrated in vacuo. The residual solid was dissolved in water (3 mL) and filtered. Filtrate pH was adjusted from 9.8 to 5.5 by careful addition of concentrated HCl and allowed to st

32、and for 30 min. The solid thus obtained was washed with water (3* 2 mL) and dried under high vacuum over P2O5 at 46 to give 28 mg (40%) of L-homocystine 13 as an off-white solid. 1H NMR (D2O/NaOD): 3.15 (dd, J=7.4, 5.8 Hz, 2H), 2.58 (t, J=8.0 Hz, 4H), 1.901.64 (m, 4H); 13C NMR (D2O/NaOD): 183.13, 55

33、.40, 34.78, 34.73;2.1.2 3.2 Synthesis of the key intermediate of the novel rennin inhibitor AliskirenReferences: Helvetica Chimica Acta, 86 (2003), 28482870.(2S,5R)-2,5-Dihydro-3,6-dimethoxy-2-(2S)-2-4-methoxy-3-(3-methoxypropoxy)phenylmethyl-3-methylbutyl-5-(1-methylethyl)pyrazine (2S,5R,2_S)-13a).

34、 To a solution of (2R)-2,5-dihydro-3,6-dimethoxy-2-(1-methylethyl) pyrazine (R)-12a; 51.3 g, 0.279 mol) in THF (0.5 l) at 75 was added dropwise 1.6 M BuLi in hexane (174 ml, 0.279 mol) during 45 min. After additional stirring for 30 min at 75 , a solution of (R)-1 (66.8g, 0.186 mol) in THF (0.3 L) w

35、as added dropwise over 30 min. The mixture was stirred for 2 h at 75 and then for 18h at 20 . After evaporation, the residue was partitioned between AcOEt (3 * 1 L) and H2O (3 * 1 L). The org. layers were washed with brine (1 L), combined, dried (MgSO4), and evaporated. The residue was dried under h

36、igh vacuum (50 /0.02 bar) to remove excess (R)-3 and purified by FC (AcOEt/hexane 1 :5): crude (2S,5R,2_S)-13a (78.0 g, 91%). TLC (hexane/AcOEt 2 : 1): Rf 0.34. 1H-NMR: 6.65 6.80 (m, 3 H); 4.10 (t, J_7, 2 H); 3.90 4.0(m, 2 H); 3.83 (s, 3 H); 3.69 (s, 6 H); 3.57 (t, J_7, 2 H); 3.35 (s, 3 H); 2.70 (dd

37、, J_4, 13.5, 1 H); 2.42 (dd, J_7.5, 13.5, 1 H); 2.28( m, 1 H); 2.10 (m, 2 H); 1.8 5(m, 1 H); 1.45 1.70 (m, 3 H); 1.04 (d, 3 H); 0.80 (m, 6 H); 0.65 (d, 3 H). FAB-MS: 463 (100, M-H), 419 (60), 209 (35), 183 (60), 141 (85).To a stirred solution of (2S, 5R, 2_S)-3 (77.5 g, 0.167 mol) in MeCN (0.67 L) a

38、t room temperature was added 1 HCl (0.67 l, 0.670 mol), and stirring was continued for 1.5 h. The mixture was poured into ice-cooled saturated aqueous NaHCO3 solution and extracted with CH2Cl2 (3* 1 L). Evaporation of the org. phase gave 82 g of a pale yellow oil. The valine methyl ester by-product

39、was removed by evaporation under high vacuum (50_/0.02 bar). FC (CH2Cl2/MeOH/conc. NH3 solution 950 :50 : 1) of the oily residue gave methyl (2S,4S)-2-amino-4-4-methoxy-3-(3-methoxypropoxy) benzyl-5-methylhexanoate (55.5 g, 90%). Oil. TLC (CH2Cl2/ MeOH/conc. NH3 solution 700 : 50 : 1): Rf 0.41. 1H-N

40、MR: 6.65 6.80 (m, 3 H); 4.10 (t, J_7, 2 H); 3.83 (s, 3 H);3.67 (s, 3 H); 3.57 (t, J_7, 2 H); 3.34 (s, 3 H); 3.32 (m, 1 H); 2.50 (m, 2 H); 2.10 (m, 2 H); 1.75 (m, 2 H); 1.2 1.65 (m, 4 H); 0.86 (m, 6 H). To a stirred solution of this material (55.0 g, 0.149 mol) in CH2Cl2 (450 ml) at 0_ were added Et3

41、N (35.6 ml, 0.208 mol ) and Boc2O (42.3 g, 0.194 mol) in CH2Cl2 (100 ml). The mixture was stirred for 20 h at room temperature Evaporation and FC (CH2Cl2_CH2Cl2/Et2O 8: 2) afforded, after recrystallization, pure (2S,4S)-17 (57.0 g, 82%) white solid. TLC (AcOEt/hexane 1 : 1): Rf 0.45. M.p. 70 71 (fro

42、m Et2O/hexane). 1H-NMR: 6.66 6.79 (m, 3 H); 4.87 (d, 1 H); 4.36 (m, 1 H); 4.10 (t, J_7, 2 H); 3.83 (s, 3 H); 3.67(s, 3 H); 3.57 (t, J_7, 2 H); 3.34 (s, 3 H); 2.64 (m, 1 H); 2.44 (m, 1 H); 2.10 (m, 2 H); 1.50 1.78( m, 4 H); 1.45(s, 9 H); 0.83 (m, 6 H). 2.1.3 Efficient syntheses of biologically import

43、ant amino acidTo a solution of cyclic tertiary alcohol 1 (3.5 mmol) in CHCl3 (10mL) was added powdered K2CO3 (2.90 g, 21 mmol) at 0 (for 2aand 2b) or 40 (for 2c). The mixture was stirred for 10 min, and bromine (0.90 mL, 17.5 mmol) was then added dropwise. The reaction mixture was stirred at 0 C (fo

44、r 2a and 2b) or 40 (for 2c) for 10 h. The mixture was quenched with saturated Na2S2O3 solution (10mL) and extracted with EtOAc (2 15 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The resultant residue was purified by flash chromatography (silicagel; hexanes

45、EtOAc, 10: 1) to yield 9.7-Bromo-heptan-3-one (2a)Yield: 70%; colorless oil. 1H NMR (300 MHz, CDCl3): 1.04 (t, J = 7.5 Hz, 3 H), 1.661.77 (m, 2 H), 1.801.90 (m, 2 H), 2.41 (m, 4 H), 3.39 (t, J = 6.6Hz, 2 H). 8-Bromo-octan-3-one (2b)Yield: 80%; colorless oil. 1H NMR (300 MHz, CDCl3): 1.05 (t, J = 7.2

46、 Hz, 3 H), 1.371.48 (m, 2 H), 1.551.65 (m, 2 H), 1.821.91 (m, 2 H), 2.43 (m, 4H), 3.40 (t, J = 6.6 Hz, 2 H). 9-Bromo-nonan-3-one (2c)Yield: 65%; colorless oil. IR (neat): 2936, 2859, 1715, 1458, 1111 cm1. 1H NMR (300 MHz, CDCl3): 1.04 (t, J = 7.5 Hz, 3 H), 1.241.35 (m, 2 H), 1.381.48 (m, 2 H), 1.531

47、.63 (m, 2 H), 1.791.89 (m, 2 H), 2.41 (m, 4 H), 3.39 (t, J = 6.6 Hz, 2 H). 13C NMR (75 MHz, CDCl3): 211.58, 42.11, 35.89, 33.80, 32.50, 28.30, 27.88, 23.57, 7.81. MS (EI): m/z (%) = 221 (M+, 5), 191 (24), 141 (33), 83 (60), 72 (71), 57 (100), 55 (66).Preparation of 3ac; To a stirred solution of -bro

48、moketone 2 (1.1 mmol) in benzene (5mL) was added ethyleneglycol (0.15 mL, 2.75 mmol) and p-TsOH (10 mol%, 21 mg). The mixture was heated to reflux in a DeanStark apparatus for 12 h. After being cooled to room temperature, the reaction mixture was poured into saturate NaHCO3 solution, and extracted w

49、ith Et2O (2 10 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The resultant residue was purified by flash chromatography (silica gel; petroleum etherEtOAc, 15: 1) to yield 3.2-(4-Bromo-butyl)-2-ethyl-1,3dioxlane (3a)Yield: 82%; colorless oil. IR (neat): 2947

50、, 2879, 1460, 1070 cm1; 1H NMR (300 MHz, CDCl3): 0.89 (t, J = 7.2 Hz, 3 H), 1.451.69 (m, 6 H), 1.821.92 (m, 2 H), 3.40 (t, J = 6.9 Hz, 2 H), 3.93 (s, 4 H). 13C NMR (75 MHz, CDCl3): = 111.76, 65.00, 35.68, 33.65, 32.94, 29.86, 22.48, 8.11. MS (EI): m/z (%) = 237 (7), 236 (M+, 5), 209 (59), 207 (68),

51、135 (14), 101 (100), 57 (56).2-(5-Bromo-pentyl)-2-ethyl-1,3dioxlane (3b)Yield: 80%; colorless oil. IR (neat): 2944, 2880, 1462, 1073 cm1. 1H NMR (300 MHz, CDCl3): 0.86 (t, J = 7.5 Hz, 3 H), 1.311.44 (m, 4 H), 1.561.62 (m, 4 H), 1.781.88 (m, 2 H), 3.37 (t, J = 6.9 Hz, 2 H), 3.90 (s, 4 H). 13C NMR (75

52、 MHz, CDCl3): 111.78, 64.89, 36.37, 33.70, 32.70, 29.77, 28.34, 22.86, 8.04. MS (EI): m/z (%) = 250 (M+ +1, 3), 221 (37), 101 (100), 69 (30), 57(34).2-(6-Bromo-hexyl)-2-propyl-1,3dioxlane (3c)Yield: 95%; colorless oil. IR (neat): 2940, 1460, 1072 cm1. 1H NMR (300 MHz, CDCl3): 0.90 (t, J = 7.5 Hz, 3

53、H), 1.251.49 (m, 6 H), 1.571.66 (m, 4 H), 1.811.90 (m, 2 H), 3.40 (t, J = 6.9 Hz, 2 H), 3.93 (s, 4 H). 13C NMR (75 MHz, CDCl3): 111.99, 64.98, 36.56, 33.95, 32.71, 29.83, 29.02, 28.12, 23.58, 8.13. MS (EI): m/z (%) = 265 (M+ + 1), 3, 235 (13), 101 (100), 83, (11), 57 (47).Preparation of 5ac;A soluti

54、on of LDA (2.2 mL, 0.5 M in THF, 1.1 mmol) was added to a stirred solution of the bislactim ether 4 (1.0 mmol) in THF (3 mL) at 78 C, which was stirred for 20 min. Then, a solution of alkyl bromide 3 (300 mg, 1.1 mmol) in THF (2 mL) was added dropwise. The reaction mixture was warmed to 50 C and sti

55、rred for 16h. The solution was quenched with phosphate buffer solution (pH7). The crude reaction mixture was warmed to room temperature, and the solvent was removed in vacuo. The resulting material was diluted with water and extracted with EtOAc (2 10 mL). The combined organic layers were washed wit

56、h brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (silica gel; hexanesEtOAc, 10: 1) to give pure 5a. 2-4-(2-Ethyl-1,3dioxolan-2-yl)-butyl-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (5a) Yield: 80%; colorless oil. IR (neat): 2946, 2874, 1696, 1462, 1437, 123

57、8, 1196, 1142, 1076, 1011 cm1. 1H NMR (300 MHz, CDCl3): 0.68 (d, J = 6.6 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3 H), 1.04 (t, J = 6.9 Hz, 3 H), 1.161.40 (m, 4 H),1.561.65 (m, 4 H), 1.661.86 (m, 2 H), 2.212.31 (m, 1 H), 3.68 (s, 3 H), 3.69 (s, 3 H), 3.92 (s, 4 H), 3.93 (m, 1 H), 3.994.04 (m, 1H). 13C NMR (7

58、5 MHz, CDCl3): = 163.89, 163.51, 112.02, 64.97, 60.67, 55.38, 52.36, 36.68, 34.11, 31.65, 29.88, 24.78, 23.66, 19.05,16.54, 8.12. MS (EI): m/z (%) = 340 (M+, 15), 297 (15), 279 (20), 253 (21), 239 (28), 183 (22), 141 (30), 101 (100), 57 (35), 55 (20). HRMS (EI): m/z calcd for C18H32N2O4, 340.2362; 2-5-(2-Ethyl-1,3dioxolan-2-yl)-pentyl-5-isopropyl-3,6-dimethoxy-2,5-di