2，3-二取代环丙烷氨基酸衍生物的不对称合成方法研究
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摘要
1-氨基环丙烷-1-羧基及其衍生物是目前有机化学中倍受关注的领域。这类化合物具有独特的生物活性和潜在限制多肽构象的用途。
环丙烷氨基酸类化合物主要分为2-取代，2,2-二取代，2,3-二取代三大类。本课题组已对2,3-二芳基取代的环丙烷氨基酸的合成方法及产物的立体选择性进行了深入的研究；本论文将对2-烷基-3-芳基二取代环丙烷氨基酸的不对称合成方法进行深入探讨。
论文分综述和实验两个部分。
综述部分系统地概述了D-甘露醇作为手性源化合物在有机合成中的应用，主要是从（1）合成环丙烷氨基酸及其衍化物、合成环丙烷类化合物、合成α-取代甘氨酸类化合物（2）合成天然产物（3）和金属及类金属元素配位等三个方面来阐述，并列举D-甘露醇在各个方面应用的例子。
实验部分的内容包括两个方面
（一）原料的制备和卡宾加成成环
我们在实验室原有的工作基础上，以价廉易得的D-甘露醇为原料，在氯化锌催化下先与丙酮反应，得到1,2:5,6-二缩丙酮甘露醇；产物与四乙酸铅、马尿酸、乙酐于THF中回流18 h完成一釜二步反应，纯化后得到含有手性碳原子的环丙烷氨基酸前体(Z)-2苯基-4-[ (S)-2,3-O-(异丙叉) ]丙叉噁唑-5-酮，前体中的手性碳原子可作为环丙烷氨基酸衍生物不对称合成的手性源；所得前体再分别与芳基重氮甲烷反应，即得螺环丙烷衍生物；再经甲醇解开环后，得到相应的氨基和羧基均被保护的环丙烷氨基酸衍生物。
（二）环丙烷氨基酸衍生物的转化制备
环丙烷氨基酸衍生物具有丙酮缩二醇的结构单元，经酸性水解后得到含邻二羟基结构单元的衍生物；对二醇进行不彻底氧化，可以得到含醛基的环丙烷氨基酸衍生物；对所得产物进行氧化和还原就分别得到含羧基衍生物和含羟甲基衍生物；接下去对羟甲基衍生物依次进行氯代和还原反应就可以得到2-甲基取代环丙烷氨基酸衍生物；最后的产物进行水解就可以得到环丙烷氨基酸盐。
所得的21个产物都用红外光谱、氢核磁共振谱等现代分析手段进行了表征和确认。
实验结果表明，以上的合成方法具有合成原料易得、反应条件温和、操作简便、产率高等优点，我们在实验中成功地在环丙烷氨基酸衍生物前体中引入了手性碳原子，以此为手性源实现了环丙烷氨基酸衍生物地不对称合成；我们利用产物中潜在的邻二羟基结构单元，经酸性水解、氧化裂解和官能团转化后，合成了一系列带有不同官能团的环丙烷氨基酸衍生物。
Since the first report on the isolation of 1-amino-1-cyclopropane- carboxylic acid (AAC), the sythesis of this compound and its derivatives have attracted special interest,because of their biological activity and potencial use in conformationally restricted pepties.
ACCs, conventionally classified as 2-substituted, 2,2-disubstituted and 2,3-disubstituted.We have reported our studies on the stereoselective synthesis of 2,3-diarylsubstituted ACCs. In this context,extensive efforts have been diverted toward the asymmetric sythesis of 2-alkyl-3-aryl- disubstituted ACCs.
In the review part of the dissertation,we summarized up the applica- tions of D-mannital in the organic synthesis as a potentially chiral material. Then we give some representative examples of organic synthesis started from D-mannital.We organize them in three routes as following: (1) Synthesis of 1-amino-1-cyclopropanecarboxylic acid and its derivatives; Synthesis of cyclopropane and its derivatives; Synthesis of а-substituted glycine (2) Synthesis of natural compound (3) Coordination with metal and kinds of metallic element.
In the experimental part two sections are covered. The first one is dealed with the preparation of starting material and the construction of precursor of cyclopropane derivatives. Our previous studies have covered the first section. 6 new products(each contains four chiral carbon atoms) are synthesized and characterized. Starting from the easily available D-mannitol, reacted with acetone in the presence of anhydrous zinc chloride to give 1,2:5,6-di-O-isopropylidene-D-mannitol. Then the protect- ed D-mannitol, mixed with lead tetraacetate, hippuric and acetic anhydride, was refluxed in tetrahydrofuran for 18 h in a one-pot two steps reaction to afford a chiral precursor(Z)-2-phenyl-4-[(S)-2,3-O-(isopropylidene)]-prop- ylidene-5(4H)-oxazolones. This precursor reacted with aryldia- zomethane in toluene to provide three spirocyclopropane derivatives. Ring opening of these spirocyclopropane derivatives in Anhydrous methanol containing catalytic amounts of sodium methoxide afforded three corresponding benz- oylamino methyl esters.
In section two we studied on the synthesis of the 2,3-disubstituted
ACCs. The products obtained in the first section can be easily converted to 2-glycol-3-aryl- disubstituted ACCs by acid hydrolysis of the acetonide in quantitative yields. The uncompletely oxidative cleavage of the diols with lead tetra-acetate in anhydrous tetrahydrofuran in low temperature afford aldehydes in over 90% yields. Following the oxidation of the aldehydes with hydrogen peroxide 30% water solution, carboxylates are obtained in good yields(83-86%). Reductions of the aldehydes were carried out in methanol with sodium borohydride in 0.2mol/L sodium hydroxide to afford substituted methanols. The chloridization of the substituted methanols with triphenylphosphine in carbon tetrachloride give chloromethano derivatives, followed with the reductions of the chloromethano derivatives to afford 2-alkyl-3-aryl-disubstituted ACCs in high yields (over 90%). The last step of the experimental part was the acid hydrolysis of the previous products to give 2-alkyl-3-aryl-disubstituted ACC in good yields.
All the 21 new products were characterized by IR and 1H-NMR.
The results indicated that the strategy using in our synthesis of 2-alkyl-3-aryl-disubstituted ACCs has significant advantages: common av- ailable materials, mild reaction condition, simple operations, high yields. The key step in our synthesis procedure: we succeeded in incorporating a chiral center into the ACCs’ precursor. Because of the existent of the potential diols in the products,they can be converted to many other desired ACCs by acid hydrolysis of the acetonide, following the oxidative cleavage of the diol and the function group inversion of the resulting oxidative products.
环丙烷氨基酸类化合物主要分为2-取代，2,2-二取代，2,3-二取代三大类。本课题组已对2,3-二芳基取代的环丙烷氨基酸的合成方法及产物的立体选择性进行了深入的研究；本论文将对2-烷基-3-芳基二取代环丙烷氨基酸的不对称合成方法进行深入探讨。
论文分综述和实验两个部分。
综述部分系统地概述了D-甘露醇作为手性源化合物在有机合成中的应用，主要是从（1）合成环丙烷氨基酸及其衍化物、合成环丙烷类化合物、合成α-取代甘氨酸类化合物（2）合成天然产物（3）和金属及类金属元素配位等三个方面来阐述，并列举D-甘露醇在各个方面应用的例子。
实验部分的内容包括两个方面
（一）原料的制备和卡宾加成成环
我们在实验室原有的工作基础上，以价廉易得的D-甘露醇为原料，在氯化锌催化下先与丙酮反应，得到1,2:5,6-二缩丙酮甘露醇；产物与四乙酸铅、马尿酸、乙酐于THF中回流18 h完成一釜二步反应，纯化后得到含有手性碳原子的环丙烷氨基酸前体(Z)-2苯基-4-[ (S)-2,3-O-(异丙叉) ]丙叉噁唑-5-酮，前体中的手性碳原子可作为环丙烷氨基酸衍生物不对称合成的手性源；所得前体再分别与芳基重氮甲烷反应，即得螺环丙烷衍生物；再经甲醇解开环后，得到相应的氨基和羧基均被保护的环丙烷氨基酸衍生物。
（二）环丙烷氨基酸衍生物的转化制备
环丙烷氨基酸衍生物具有丙酮缩二醇的结构单元，经酸性水解后得到含邻二羟基结构单元的衍生物；对二醇进行不彻底氧化，可以得到含醛基的环丙烷氨基酸衍生物；对所得产物进行氧化和还原就分别得到含羧基衍生物和含羟甲基衍生物；接下去对羟甲基衍生物依次进行氯代和还原反应就可以得到2-甲基取代环丙烷氨基酸衍生物；最后的产物进行水解就可以得到环丙烷氨基酸盐。
所得的21个产物都用红外光谱、氢核磁共振谱等现代分析手段进行了表征和确认。
实验结果表明，以上的合成方法具有合成原料易得、反应条件温和、操作简便、产率高等优点，我们在实验中成功地在环丙烷氨基酸衍生物前体中引入了手性碳原子，以此为手性源实现了环丙烷氨基酸衍生物地不对称合成；我们利用产物中潜在的邻二羟基结构单元，经酸性水解、氧化裂解和官能团转化后，合成了一系列带有不同官能团的环丙烷氨基酸衍生物。
Since the first report on the isolation of 1-amino-1-cyclopropane- carboxylic acid (AAC), the sythesis of this compound and its derivatives have attracted special interest,because of their biological activity and potencial use in conformationally restricted pepties.
ACCs, conventionally classified as 2-substituted, 2,2-disubstituted and 2,3-disubstituted.We have reported our studies on the stereoselective synthesis of 2,3-diarylsubstituted ACCs. In this context,extensive efforts have been diverted toward the asymmetric sythesis of 2-alkyl-3-aryl- disubstituted ACCs.
In the review part of the dissertation,we summarized up the applica- tions of D-mannital in the organic synthesis as a potentially chiral material. Then we give some representative examples of organic synthesis started from D-mannital.We organize them in three routes as following: (1) Synthesis of 1-amino-1-cyclopropanecarboxylic acid and its derivatives; Synthesis of cyclopropane and its derivatives; Synthesis of а-substituted glycine (2) Synthesis of natural compound (3) Coordination with metal and kinds of metallic element.
In the experimental part two sections are covered. The first one is dealed with the preparation of starting material and the construction of precursor of cyclopropane derivatives. Our previous studies have covered the first section. 6 new products(each contains four chiral carbon atoms) are synthesized and characterized. Starting from the easily available D-mannitol, reacted with acetone in the presence of anhydrous zinc chloride to give 1,2:5,6-di-O-isopropylidene-D-mannitol. Then the protect- ed D-mannitol, mixed with lead tetraacetate, hippuric and acetic anhydride, was refluxed in tetrahydrofuran for 18 h in a one-pot two steps reaction to afford a chiral precursor(Z)-2-phenyl-4-[(S)-2,3-O-(isopropylidene)]-prop- ylidene-5(4H)-oxazolones. This precursor reacted with aryldia- zomethane in toluene to provide three spirocyclopropane derivatives. Ring opening of these spirocyclopropane derivatives in Anhydrous methanol containing catalytic amounts of sodium methoxide afforded three corresponding benz- oylamino methyl esters.
In section two we studied on the synthesis of the 2,3-disubstituted
ACCs. The products obtained in the first section can be easily converted to 2-glycol-3-aryl- disubstituted ACCs by acid hydrolysis of the acetonide in quantitative yields. The uncompletely oxidative cleavage of the diols with lead tetra-acetate in anhydrous tetrahydrofuran in low temperature afford aldehydes in over 90% yields. Following the oxidation of the aldehydes with hydrogen peroxide 30% water solution, carboxylates are obtained in good yields(83-86%). Reductions of the aldehydes were carried out in methanol with sodium borohydride in 0.2mol/L sodium hydroxide to afford substituted methanols. The chloridization of the substituted methanols with triphenylphosphine in carbon tetrachloride give chloromethano derivatives, followed with the reductions of the chloromethano derivatives to afford 2-alkyl-3-aryl-disubstituted ACCs in high yields (over 90%). The last step of the experimental part was the acid hydrolysis of the previous products to give 2-alkyl-3-aryl-disubstituted ACC in good yields.
All the 21 new products were characterized by IR and 1H-NMR.
The results indicated that the strategy using in our synthesis of 2-alkyl-3-aryl-disubstituted ACCs has significant advantages: common av- ailable materials, mild reaction condition, simple operations, high yields. The key step in our synthesis procedure: we succeeded in incorporating a chiral center into the ACCs’ precursor. Because of the existent of the potential diols in the products,they can be converted to many other desired ACCs by acid hydrolysis of the acetonide, following the oxidative cleavage of the diol and the function group inversion of the resulting oxidative products.
引文
1. Wust, H. H.; Bardenhagen, J.; et al. Liebigs. Ann.Chem. 1985, (9):1825
2. Katoch Rita; Trivedi,G. K.; et al. Bioorganic & Medicinal Chemistry, 1999, 7, 2753
3. Rose, M. J.; Joan Rife.; et al. Tetrahedron:Asymmetry, 1995, 6(8), 1849-1852
4. Schmidt, U.; Lieberknecht, U.; et al. Synthesis, 1991, 49
5. Carlos Cativiela; Maria, D.D.; et al. Tetrahedron:Asymmetry, 1995, 6, 177-182
6. Carlos Cativiela; Maria, D.D.; et al. Tetrahedron:Asymmetry, 1995, 6, 2076-2082
7. Geoffrey, D.C.; Juma, R.A.; et al. Tetrahedron:Asymmetry, 2003 , 14, 1211- 1222
8. Furakawa, J.; Kawabata, N.; et al. Tetrahedron Lett, 1966, 7, 3353-3354
9. Furakawa, J.; Kawabata, N.; et al. Tetrahedron Lett, 1969, 25, 2647-2659
10. Morikawa, T.; Sasaki, H.; et al. J.Org.Chem. 1994, 59, 97-103
11. Zhao, Y.; Yang, T.; et al. Tetrahedron Lett, 1994, 35, 5405-5408
12. Newman, M.S.; Renall, M. J.Am. Chem.Soc. 1945, 67, 1621
13. Alain Krief; Laurent Provins; et al. Tetrahedron Lett, 1998, 39, 1437-1440
14. Badorrey Ramon; Cativiela Carlos; et al. Synthesis, 1998, 4, 454
15. a) Rando, R.R. Biochemistry, 1974, 13, 3859
b) Rando, R.R. Acc.Chem.Res. 1975, 8, 281
c) Rando, R.R. ; Relyea, N.; Cheng, L. J.Biol.Chem. 1976, 251, 3306
16. Havlidek, L.; Hanus, J. Collect.Czech.Chem.Commun. 1991, 56, 1365
17. Badorrey, R.; Cativiela, C.; Maria, D.D.; et al. Tetrahedon, 1997, 53, 1411
18. Badorrey, R.; Cativiela,C.; Maria, D.D.; et al. Tetrahedron, 1999, 55, 14145- 14160
19. 曾和平. 甘露醇在天然产物合成中的应用. 化学试剂，1994，16（2），103-104
20. Shing, T. K .M. Tetrahedron, 1988, 44, 7261
21. Hecker, S. J.; Minich, M.L.; Lackey, K. J.Org.Chem. 1990, 55, 4904
22. Devine, P.N.; Oh, T.T. Tetrahedron Lett;1991,32(7),883
23. Jung, M.E.; Shaw, T.J. J.Am.Chem.Soc. 1980, 102, 6304
24. 张生勇; 戴寿荣; 孙晓莉. 用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇. 有机化学, 1999, 19, 59-62
25. Quinoa, E.; Kho, E.; Manes, L.V. J.Org.Chem. 1986, 51, 4260
26. Kondo, K.; Yamada, Y.; Sugamura, K. J.Antibiot. 1989, 42, 1873
27. Takano, S.; Ogasaware, K. J.Synth.Org.Chem.Jpn. 1982, 40, 1037
28. Ireland, R.E.; Anderson, R.C.; et al. J.Am.Chem.Soc. 1983, 105, 1988
29. Takano Seiichi; Kurotaki Ayako; et al. Synthesis, 1986, 5, 403-406
30. 曾和平. 旋光活性内酯化合物研究Ⅴ.4-羟甲基丁烯-2-内酯的合成. 化学试剂, 1995, 17, 47-48
31. 曾和平. 2,3-二羟基-4-羟甲基丁内酯的合成. 精细化工, 1994, 11, 41-43
32. Sung Ho Kang; Wan Joo Kim Tetrahedron Lett, 1989, 30, 5915-5918
33. Vedejs, E.; Wu, E.S. Tetrahedron Lett, 1973, 24, 3793
34. Haines, A.H. Carbohydrate Res. 1965, 1, 214
35. Corey, E.J.; Winter, R.A. J. Am.Chem.Soc. 1963, 85, 2677
36. Fieser, L.F.; Fieser, M. Reagents for Organic Synthesis, Vol.1, p.979
37. David, S.; Hanessisn, S. Tetrahedron, 1985, 41, 643
38. Dasgupta, F.; Garegg, P.J. Synthesis, 1988, 8, 626
39. Garegg, P.J.; Lindberg, B. Carbohydrate Res. 1988, 173, 205
40. Marzi, M.; Misiti, D. Tetrahedron Lett, 1989, 30, 6075-6076
41. Jersld, S.B.; Peter. H.;et al. J.Org.Chem. 1990, 55, 3129-3137
42. 周喜春; 严慧; 吴采樱. 手性冠醚聚硅氧烷固定相的制备及其气相色谱性能.分析化学; 1996, 24, 1123-1128
43. Krief, A.; Dumont, W.; et al. Tetrahedron, 1989, 45, 3039-3052
44. L.J.Rubin.; H.A.Lardy.; H.O.L.Fischer. J.Am.Chem.Soc. 1952, 74, 425
45. 詹天荣; 宋金明. 甘露醇的药用研究进展. 中国海洋药物; 2003, 3, 57-61
46. 赵桂芝; 王桂梅. 镇咳药左羟丙哌嗪的合成研究. 中国医药工业杂志, 1998, 29, 485
47. 王光星; 王琳; 贾宝和. 抗病毒化合物S-DHPA的合成及其对SAH水解的抑制活性. 中国药物化学杂志, 1997, 7, 9
48. 国外药讯, 1989(4): 8
49. Ginai, R.; Marinone, E.; Melillo, G..; et al A rzneim-Forsch, 1988, 38(4):1139
50. Fiorini; et al. EP, 60, 595, 1982 (CA 98, 89916y)
51. Milkale; et al. Tetrahedron, 1992, 48, 319-321
52. a) Kolb, H.; et al. Tetrahedron:Asymmetry, 1993, 4, 133-141
b) Son, C. E.; et al. Tetrahedron:Asymmetry, 1995, 6, 1063-1066
53. M. kitamura.; et al. Tetrahedron Lett, 1988, 29, 155-156
54. Renaud; et al. Synthesis, 1986, 4, 424-426
55. Neil Baggett; Peter Stribbiehill. J.C.S.PerkinⅠ, 1977, 1123-1126
56. Ken-ichi Fujita; Kazuhisa Murata. Tetrahedron Lett, 1995, 36, 5219-5222
参考文献（实验部分）
1. Allert, A.; Boyer , R. J. Chem. Soc. 1949, 1148-1152.
2. Farnum, D. G. J. Org. Chem. 1963, 28 (3 ), 870.
3. Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry. 5th ed.; Longman:
London. 1989, 1156.
4. Morpain, C.; Nasser, B.; et al. Org. Prep. Proced. Int. 1990, 22 (4), 540-543.
5. Combs, A. P.; Armstrong, R. W. Tetrahedron Letters. 1992, 33 (43), 6419-6422.
6. a) Cativiela, C.; Diaz-de-Villegas, M. D.; Jimenez, A. L. Tetrahedron. 1994, 50 (30), 9157-9166.
b)Arenal, L.; Bernabe, M.; Fernandez-Alvarez, E; et al. Synthesis. 1985, (8), 773-775.
7. King, S,.W.; Riotdan, J. M.; Holt, E. M.; et al. J. Org. Chem. 1982, 47 (17), 3270-3273.
8. Carlos Cativiela; MariaD. Diaz-de-Villegas; Ana I. Jimenez;Tetrahedron:Asymmet- ry. 1995, 6 (8), 2067-2072.
9. 潘成学. 广西师范大学硕士研究生学位论文，2003年5月
10. Jimwnez, A. I.; Lopez, P.; Oliveros, L.; Cativiela, C. Tetrahedron. 2001, 57, 6019
2. Katoch Rita; Trivedi,G. K.; et al. Bioorganic & Medicinal Chemistry, 1999, 7, 2753
3. Rose, M. J.; Joan Rife.; et al. Tetrahedron:Asymmetry, 1995, 6(8), 1849-1852
4. Schmidt, U.; Lieberknecht, U.; et al. Synthesis, 1991, 49
5. Carlos Cativiela; Maria, D.D.; et al. Tetrahedron:Asymmetry, 1995, 6, 177-182
6. Carlos Cativiela; Maria, D.D.; et al. Tetrahedron:Asymmetry, 1995, 6, 2076-2082
7. Geoffrey, D.C.; Juma, R.A.; et al. Tetrahedron:Asymmetry, 2003 , 14, 1211- 1222
8. Furakawa, J.; Kawabata, N.; et al. Tetrahedron Lett, 1966, 7, 3353-3354
9. Furakawa, J.; Kawabata, N.; et al. Tetrahedron Lett, 1969, 25, 2647-2659
10. Morikawa, T.; Sasaki, H.; et al. J.Org.Chem. 1994, 59, 97-103
11. Zhao, Y.; Yang, T.; et al. Tetrahedron Lett, 1994, 35, 5405-5408
12. Newman, M.S.; Renall, M. J.Am. Chem.Soc. 1945, 67, 1621
13. Alain Krief; Laurent Provins; et al. Tetrahedron Lett, 1998, 39, 1437-1440
14. Badorrey Ramon; Cativiela Carlos; et al. Synthesis, 1998, 4, 454
15. a) Rando, R.R. Biochemistry, 1974, 13, 3859
b) Rando, R.R. Acc.Chem.Res. 1975, 8, 281
c) Rando, R.R. ; Relyea, N.; Cheng, L. J.Biol.Chem. 1976, 251, 3306
16. Havlidek, L.; Hanus, J. Collect.Czech.Chem.Commun. 1991, 56, 1365
17. Badorrey, R.; Cativiela, C.; Maria, D.D.; et al. Tetrahedon, 1997, 53, 1411
18. Badorrey, R.; Cativiela,C.; Maria, D.D.; et al. Tetrahedron, 1999, 55, 14145- 14160
19. 曾和平. 甘露醇在天然产物合成中的应用. 化学试剂，1994，16（2），103-104
20. Shing, T. K .M. Tetrahedron, 1988, 44, 7261
21. Hecker, S. J.; Minich, M.L.; Lackey, K. J.Org.Chem. 1990, 55, 4904
22. Devine, P.N.; Oh, T.T. Tetrahedron Lett;1991,32(7),883
23. Jung, M.E.; Shaw, T.J. J.Am.Chem.Soc. 1980, 102, 6304
24. 张生勇; 戴寿荣; 孙晓莉. 用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇. 有机化学, 1999, 19, 59-62
25. Quinoa, E.; Kho, E.; Manes, L.V. J.Org.Chem. 1986, 51, 4260
26. Kondo, K.; Yamada, Y.; Sugamura, K. J.Antibiot. 1989, 42, 1873
27. Takano, S.; Ogasaware, K. J.Synth.Org.Chem.Jpn. 1982, 40, 1037
28. Ireland, R.E.; Anderson, R.C.; et al. J.Am.Chem.Soc. 1983, 105, 1988
29. Takano Seiichi; Kurotaki Ayako; et al. Synthesis, 1986, 5, 403-406
30. 曾和平. 旋光活性内酯化合物研究Ⅴ.4-羟甲基丁烯-2-内酯的合成. 化学试剂, 1995, 17, 47-48
31. 曾和平. 2,3-二羟基-4-羟甲基丁内酯的合成. 精细化工, 1994, 11, 41-43
32. Sung Ho Kang; Wan Joo Kim Tetrahedron Lett, 1989, 30, 5915-5918
33. Vedejs, E.; Wu, E.S. Tetrahedron Lett, 1973, 24, 3793
34. Haines, A.H. Carbohydrate Res. 1965, 1, 214
35. Corey, E.J.; Winter, R.A. J. Am.Chem.Soc. 1963, 85, 2677
36. Fieser, L.F.; Fieser, M. Reagents for Organic Synthesis, Vol.1, p.979
37. David, S.; Hanessisn, S. Tetrahedron, 1985, 41, 643
38. Dasgupta, F.; Garegg, P.J. Synthesis, 1988, 8, 626
39. Garegg, P.J.; Lindberg, B. Carbohydrate Res. 1988, 173, 205
40. Marzi, M.; Misiti, D. Tetrahedron Lett, 1989, 30, 6075-6076
41. Jersld, S.B.; Peter. H.;et al. J.Org.Chem. 1990, 55, 3129-3137
42. 周喜春; 严慧; 吴采樱. 手性冠醚聚硅氧烷固定相的制备及其气相色谱性能.分析化学; 1996, 24, 1123-1128
43. Krief, A.; Dumont, W.; et al. Tetrahedron, 1989, 45, 3039-3052
44. L.J.Rubin.; H.A.Lardy.; H.O.L.Fischer. J.Am.Chem.Soc. 1952, 74, 425
45. 詹天荣; 宋金明. 甘露醇的药用研究进展. 中国海洋药物; 2003, 3, 57-61
46. 赵桂芝; 王桂梅. 镇咳药左羟丙哌嗪的合成研究. 中国医药工业杂志, 1998, 29, 485
47. 王光星; 王琳; 贾宝和. 抗病毒化合物S-DHPA的合成及其对SAH水解的抑制活性. 中国药物化学杂志, 1997, 7, 9
48. 国外药讯, 1989(4): 8
49. Ginai, R.; Marinone, E.; Melillo, G..; et al A rzneim-Forsch, 1988, 38(4):1139
50. Fiorini; et al. EP, 60, 595, 1982 (CA 98, 89916y)
51. Milkale; et al. Tetrahedron, 1992, 48, 319-321
52. a) Kolb, H.; et al. Tetrahedron:Asymmetry, 1993, 4, 133-141
b) Son, C. E.; et al. Tetrahedron:Asymmetry, 1995, 6, 1063-1066
53. M. kitamura.; et al. Tetrahedron Lett, 1988, 29, 155-156
54. Renaud; et al. Synthesis, 1986, 4, 424-426
55. Neil Baggett; Peter Stribbiehill. J.C.S.PerkinⅠ, 1977, 1123-1126
56. Ken-ichi Fujita; Kazuhisa Murata. Tetrahedron Lett, 1995, 36, 5219-5222
参考文献（实验部分）
1. Allert, A.; Boyer , R. J. Chem. Soc. 1949, 1148-1152.
2. Farnum, D. G. J. Org. Chem. 1963, 28 (3 ), 870.
3. Vogel, A. I. Vogel’s Textbook of Practical Organic Chemistry. 5th ed.; Longman:
London. 1989, 1156.
4. Morpain, C.; Nasser, B.; et al. Org. Prep. Proced. Int. 1990, 22 (4), 540-543.
5. Combs, A. P.; Armstrong, R. W. Tetrahedron Letters. 1992, 33 (43), 6419-6422.
6. a) Cativiela, C.; Diaz-de-Villegas, M. D.; Jimenez, A. L. Tetrahedron. 1994, 50 (30), 9157-9166.
b)Arenal, L.; Bernabe, M.; Fernandez-Alvarez, E; et al. Synthesis. 1985, (8), 773-775.
7. King, S,.W.; Riotdan, J. M.; Holt, E. M.; et al. J. Org. Chem. 1982, 47 (17), 3270-3273.
8. Carlos Cativiela; MariaD. Diaz-de-Villegas; Ana I. Jimenez;Tetrahedron:Asymmet- ry. 1995, 6 (8), 2067-2072.
9. 潘成学. 广西师范大学硕士研究生学位论文，2003年5月
10. Jimwnez, A. I.; Lopez, P.; Oliveros, L.; Cativiela, C. Tetrahedron. 2001, 57, 6019
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