INTRODUCTION:

Alkaloid compounds have been found to possess a broad range of biological and pharmaceutical activities.^1-10 In recent years, polyhydroxylated indolizidine alkaloids have been found to possess a broad range of biological activities such as immunoregulatory activity, anti-HIV activity, antiviral, antitumor and anticancer activity.^11-19 This is due to the structure of these compounds, which are stereochemically rich (Figure 1).

Figure 1: Some polyhydroxylated indolizidine alkaloids

Swainsonine is an example of a polyhydroxylated indolizidine alkaloid containing a sp³ hybridised nitrogen atom and three hydroxyl groups. It has four stereogenic centres at C-1, C-2, C-8 and C-9, and therefore could exist as one of sixteen stereoisomers. (-)-Swainsonine 1 is a natural product, whereas (+)-swainsonine 6 is a non-natural product (Figure 2).

Figure 2: Structure of (-)-Swainsonine 1 and (+)-Swainsonine 6

(-)-Swainsonine 1 is a sugar analogue, the first isolation was in 1973 by Guengerich, DiMari and Broquist from the fungus plant pathogen Rhizoctonia leguminicolain,²⁰ then from the legume Swainsona canescens (Australian plant),^21,22and from fungus Metarhizium anisopliae F-3622.^23,24In addition, it was found in North American plants of genera Astragalus and Oxytropis (commonly called locoweed).^25,26

(-)-Swainsonine 1 was found to be as a potent inhibitor of Golgi enzyme mannosidase II, which is an imported enzyme for the synthesis of glycoproteins via N-linked oligosaccharides.^27-29Compound 1 is also a potent inhibitor of lysosomal α-D-mannosidase,^30,31 which lead to the accumulation of oligomannoside chains in cells exposed to the drug.^32-34In addition, the natural product 1 has been found to possess a broad range of biological activities such as immunomodulatory,^23,35,36antiviral activities,³⁷ antimetastatic,³⁸ immunoregulating,^39,40antitumor-proliferative,^41,42anticancer activities.^43,44

Skelton and White in 1980,⁴⁵ have been deduced the relative stereochemistry of (-)-swainsonine 1 by X-ray crystallography. While, the absolute configuration of 1 was determined by Harris and co-workers in 1982 depend on the biosynthetic (also called anabolism),⁴⁶two-dimensional nuclear magnetic resonance spectroscopy (2D NMR)⁴⁷ and asymmetric induction studies.⁴⁸The analogues of (-)-swainsonine 1 have been used as biochemical tools and chemotherapeutic agents against cancer,⁴⁹ HIV⁵⁰ and diabetes.⁵¹ Therefore, these interesting biological activities led to achieve many studies toward the total synthesis of (-)-swainsonine 1 and its analogues.

Total synthesis of (-)-swainsonine 1:

El Nemr⁵² has reported a review including the synthetic methods of the (-)-swainsonine 1 and its analogues since its first total synthesis until the year 2000. Following this, Pyne reported another review, which covered the literature up to 2005.⁵³Whereas, in this review, it will summarise all the total syntheses of the (-)-swainsonine 1 between 2005 and 2020 years.

Riera and co-workers,⁵⁴ reported an efficient total synthesis of (-)-swainsonine 1 enantioselectively. Their methodology was based on the use of enantiomerically pure epoxy alcohol (-)-7, which was prepared from (E)-2,4-pentadien-1-ol via Sharpless epoxidation.^55,56The product (-)-7 was used to prepare the key intermediate (+)-10 in this synthetic route (Scheme 1). Allyl carbamate derivative (+)-8 was then conveniently obtained via treatment of (-)-7 with allyl isocyanate/Et₃N. Followed by intramolecular ring opening of (+)-8 using NaHMDS afforded oxazolidinone derivative (+)-9 as a single isomer.^57,58Thereafter, the product (+)-9 was subjected in ring-closing metathesis to provide the desired intermediate (+)-10 in 56% overall yield from (-)-7 over three steps. The alkene bond at (+)-10 was hydrogenated to give 11 in 99% yield, followed by protection of the hydroxyl group with BnBr afforded 12 in 97% yield. Subsequently, hydrolysis of carbamate using basic conditions (NaOH 6.0 N) gave the corresponding amino alcohol, then the free amine was protected with a Boc group in a one-pot reaction to provide 13 in an 87% overall yield. Oxidation of primary alcohol 13 using a Dess-Martin periodinane oxidant gave the corresponding aldehyde 14 in a 98% yield. The desired unsaturated ester Z-15 was then isolated in 82% yield as a major isomer (5:1) when 14 subjected to a still reaction.⁵⁹ Next, syn-diols derivative 16 was obtained in a good yield (70%) via syn-dihydroxylation of Z-15 using OsO₄/NMO. Deprotection of the Boc protecting group at 16 using acidic conditions (Et₂O.HCl) gave amine derivative, followed by the addition of Hünig’s base, which activated the cyclisation to afford indolizin-3-one 17 in 65% yield. Hydroxyl groups at 17 were then protected with 2,2-dimethoxypropane to provide 18 in 70% yield as a single diastereoisomer. Following this, reduction of cyclic amide 18 by BH₃.SMe₂ furnished the protected desired natural product 19 in 75% yield. Finally, deprotection of two groups (benzyl and acetonide) was then successfully accomplished in a one-pot reaction by hydrogenation of 19 in the presence of PdCl₂ then HCl hydrolysis gave (-)-swainsonine 1 (Scheme 1).

Scheme 1: Enantioselective total synthesis of (-)-swainsonine 1 by Riera and co-workers

In 2006, a new enantioselective synthesis of (-)-swainsonine 1 was achieved successfully by Guo and O’Doherty (Scheme 2).⁶⁰Their approach was based on the reduction of acylfuran 23 enantioselectively to give the intermediate 24 using Noyori conditions.⁶¹The synthetic route involved 13 steps to obtain the desired (-)-swainsonine 1 starting from furan 20. The reaction between a solution of 2-lithiofuran 20 and γ-butyrolactone 21 provided furyl ketone 22 in a 74% yield. Protection of hydroxyl group at 22 was then performed using TBSCl/imidazole to afford 23 in 98% yield. Following this, asymmetric reduction of ketone at 23 using Noyori’s reagent yielded the corresponding furyl alcohol 24 with an excellent ee (>96%). Achmatowicz conditions (NBS in THF/H₂O) were then applied on 24 to give pyranone derivative 25. Thereafter, compound 25 followed by nine consecutive steps to afford the desired natural product 1in an overall yield of 17% (Scheme 2).⁶⁰

Scheme 2: Synthesis of natural product (-)-Swainsonine 1 by Guo and O'Doherty

In the same year, Ceccon, Greene and Poisson, reported a stereoselective total synthesis of (-)-swainsonine 1.⁶² Their synthetic route involved the preparation of 38 as a key intermediate via asymmetric [2+2] cycloaddition reaction (Scheme 3). The potassium alkoxide analogue of (S)-1-(2,4,6-triisopropylphenyl) ethanol 34 was treated with trichloroethylene to furnish the corresponding enol ether derivative 35 in a good yield (79%). Ynol ether acetylide 36 was then prepared by reaction between 35 and n-BuLi, which was then directly reacted with allyl iodide in a one-pot reaction, which gave ynol ether 36. Thereafter, selective reduction of the alkyne bond at 36 using DIBAL-H yielded enol ether 37, which was used in the asymmetric [2+2] cycloaddition with dichloroketene without further purification.⁶³ This afforded the key intermediate 38 in 95:5 dr, which was followed by a five sequence steps to give pyrrolidinone derivative 39 in an overall yield of 34%. The product 39 was then used to prepare 40 via allylic oxidation, but a mixture of two alcohols 40 and 41 were obtained in 49:51 dr with 56% yield. To improve the dr ratio, oxidation of alcohols 40 and 41 with a Dess-Martin reagent afforded enone forms, followed by reduction with LiAlH₄ in a one-pot reaction provided 42 and 43 in an excellent dr (92:8) with 82% yield. Disilylation of 42 then selective hydrolysis of the silyl imidate in a one-pot reactiongave 44 in 81% yield. Treatment of 44 with allyl bromide provided N-allyl derivative 45 in an excellent yield (95%). Subsequently, ring closure of 45 via cross metathesis reaction afforded the corresponding alkene 46 in 84% yield. Hydrogenation of the alkene at 46 gave the saturated analogue of 46, which was then followed by removal of the chiral auxiliary using TFA to give 47 in a very good yield (84%). Reduction and dehydration on 47 were then applied, which furnished the crude material 48. Following this, a one-pot sequence of dihydroxylation, desilylation then triacylation afforded triacetate derivative 49 in an overall yield of 41% from 48. Finally, hydrolysis of the acetyl groups yielded the desired natural product 1 in an excellent yield (97%) (Scheme 3).

Scheme 3: Ceccon, Greene and Poisson's stereoselective total synthesis of (-)-swainsonine 1

Two years later, a novel and facile stereoselective synthesis of (-)-swainsonine 1 has been reported by Shi et al.⁶⁴ This was done over five sequence steps from a chiral heterocyclic enaminoester intermediate 50 (Scheme 4). Compound 50 was synthesised according to literature procedure over six steps starting from D-erythronic acid γ-lactone.^65,66 The product 51 was prepared by reaction between 50 and methyl acrylate using a literature method.⁶⁷The conversion of 51 to the corresponding carboxylic acid 52 was achieved successfully using aqueous NaOH (20%). Thereafter, treatment of 52 with m-chloroperbenzoic acid and dicyclohexylcarbodiimide afforded a diacyl peroxide intermediate 53, which was then directly heated to reflux in toluene to give the intermediate 54. This was followed by hydrolysis of the ester to the desired product 55 in 49% yield from 52, with the desired stereochemistry at C-8. The carbonyl group at 55 was then reduced with BH₃.THF, followed by deprotection of acetonide group in a one-pot reaction using acidic conditions (HCl 6.0 N, THF), which gave the desired (-)-swainsonine 1 in a good yield (71% yield) (Scheme 4).

Scheme 4: Shi et al. Stereoselective total synthesis of (-)-swainsonine 1

In the same year, Sharma, Shah and Carver,⁶⁸ reported a scale-up synthesis of (-) swainsonine 1 over 12 steps starting from lactol 56 (Scheme 5). Treatment of 56 with 3-(carbethoxypropyl) triphenylphosphonium bromide 57 via Wittig reaction afforded 58 in a very good yield (80%). Mitsunobu conditions were applied on 58 gave a mixture of two products; desired product 59 and undesired product 60. A solution of n-Bu₄NF in THF was then added to remove the TMS protecting group at 60. This gave a mixture of 58 and 59, which was subjected to Mitsunobu conditions using 0.5 equivalents of the reagent to provide a mixture of 59 and 60. The aim of using these conditions again is to improve the yield of 59. Mitsunobu conditions were used for a third time on 59 and 60, followed by adding an extra amount of n-Bu₄NF to access the desired product 59 in 80% yield and high purity (99%, determined by HPLC). The product 59 was then heated in toluene to yield 61, which was used in the next step without further purification. Hydrolysis of the ester group at 61 under basic conditions (NaOH 2.0 N, EtOH) yielded the corresponding acid 62. Thereafter, treatment of 62 with glacial AcOH furnished 63 in a very good yield (80%). Compound 63 was treated with borane/THF, followed by the addition of solutions of NaOH (6.0 N) and H₂O₂(30%), which provided 64 in 61% yield. The desired (-)-swainsonine 1 was then prepared by treatment of 64 with IPA, which afforded 98% yield of the desired product 1 (Scheme 5).

Scheme 5: A scale-up synthesis of (-)-swainsonine 1 by Sharma, Shah and Carver

Ham and co-workers,⁶⁹reported an asymmetric synthesis of (-)-swainsonine 1 using a chiral trans-oxazoline 65, which was prepared from D-serine according to the literature method.⁷⁰ The reaction between 65 and benzyl chloroformate provided a carbamate derivative 66 in an excellent yield (96%) (Scheme 6). Dihydroxylation of the terminal alkene of 66 was then performed stereo selectively using OsO₄ to give the desired anti-diol 67 in 89% yield with 9:1 dr. The product 67 was employed to synthesise 68 in 78% yield over two steps. The hydroxyl group at 68 was then oxidised with a Dess-Martin reagent to provide the corresponding aldehyde, followed by nucleophilic addition of allyltrimethylsilane in a one-pot reaction to provide anti-amino alcohol 69 in a very good yield (83%) with 15:1 dr. Thereafter, the product 70 was prepared from 69 in 70% yield over two steps. The hydroxyl group at 70 was then activated with methanesulfonyl chloride, followed by intramolecular cyclisation and benzoate hydrolysis in a one-pot reaction, which gave 71 in a good yield (76%). Following this, mesylation then hydrogenolysis were applied on 71 to provide protected (-)-swainsonine 72 in 84% yield. Finally, the TBS and acetonide protecting groups at 72 were then removed using acidic conditions (HCl 6.0 N) to afford the natural product 1 in a very good yield (82%) (Scheme 6).

Scheme 6: Asymmetric synthesis of (-)-swainsonine 1 by Ham and co-workers

Two years later, Wardrop and Bowen,⁷¹ conducted a new total synthesis of (-)-swainsonine 1 stereoselectively over 12 steps starting from 2,3-O-isopropylidene-D-erythrose 73, which was prepared from sodium D-isoascorbate via oxidative cleavage with H₂O₂ (Scheme 7).^72,73Reduction, stereoselective allylation and selective protection were then conducted on 73 over three sequence steps to afford allylic alcohol 74 in a high dr (97:3) and a good yield (71%). This was followed by a Johnson-Claisen rearrangement of 74, which gave the ester derivative 75 in an excellent yield (99%) as a single E-isomer. Hence, deprotection of the TBS group using TBAF gave the desired alcohol 76 in 92% yield. Thereafter, double oxidation on 76 with a Dess-Martin periodinane and Pinnick conditions gave the corresponding acid, followed by treatment with isobutyl chloroformate in a one-pot reaction to afford isobutyl chloroformate 77 in a 60% yield. Cyclisation of 77 was then achieved successfully when 77 was treated with phenyliodine(III)bis(trifluoroacetate) in the presence of trifluoroacetic acid as a catalyst provided a mixture of 78 and 79 (about 6:1) in 69% yield. The desired product 79 was isolated in 60% yield from this mixture by flash column chromatography, followed by reduction of the three functional groups at 79 with LiAlH₄ to give the desired product 80 in a very good yield (85%). Appel conditions were then applied on 80, which gave indolizidine derivative 64 in 88% yield. Finally, the desired (-)-swainsonine 1 was obtained in 96% yield when 64 was treated with HCl (6.0 N) (Scheme 7).

Scheme 7: Wardrop and Bowen's total synthesis of (-)-swainsonine 1 stereoselectively

In 2013, Li et al.⁷⁴ reported a facile diastereoselective formal synthesis of (-)-swainsonine 1 using a lactone intermediate 81, which was synthesised from D-erythronolactone according to the literature procedure.⁷⁵ A one-pot sequence of reduction with DIBAL-H then Wittig reaction on 81 gave an olefin derivative 82 in a low ratio of Z/Eisomers (1.9:1), albeit in a good yield (79%) (Scheme 8). To improve this ratio, the isomerisation of the mixture 82 was then achieved successfully via treatment with AIBN and PhSH to provide a single trans olefin 83 in an 84% yield. Oxidation of the hydroxyl group at 83 using Swern conditions gave the corresponding aldehyde, followed by Wittig reaction in one-pot reaction, which afforded 84 in a very good yield (83%) and 1:2 of Z/E. The alkene bond at α,β-unsaturated ester 84 was then reduced chemoselectively with NaBH₄ to give 85 in 95% yield. Following this, reduction of ester group at 85 with LiAlH₄ afforded 86 in an excellent yield (97%). Appel conditions were employed on 86, which provided bromide 87 in 87% yield. The product 88 was then prepared in 16:1 dr and 83% yield via treatment of 87 with chlorosulfonyl isocyanate using optimised conditions.⁷⁶ Thereafter, deprotection of Bn and Cbz groups were performed when 88 reacted with BCl₃, which activates the intramolecular cyclisation to afford 89 in a 57% yield. O-Protection on 89 gave 90 in 91% yield, followed by reaction with allyl chloroformate provided 91 in a very good yield (83%). Finally, the desired (-)-swainsonine 1 was obtained according to the literature procedure in an 85% yield (Scheme 8).⁷⁷

Scheme 8: Formal synthesis of natural product (-)-swainsonine 1 by Li et al.

After a year, Singh, Manna and Panda,⁷⁸reported a new total synthesis of (-)-swainsonine 1 stereoselectively (Scheme 9). Their approach depended on using 93 as a key material in the synthetic route. The product 93 was prepared easily in some steps from (S)-Garner’s aldehyde 92.^79,80The hydrogenation of the olefin bond at 93 gave saturated form 94 in a 99% yield. Thereafter, deprotection of the TBDMS group at 94 using TBAF afforded the corresponding alcohol 95 in an excellent yield (95%).The product 95 was then oxidised with a Dess-Martin reagent to give the corresponding aldehyde, and a subsequent nucleophilic addition of vinyl magnesium bromide in a one-pot reaction provided a mixture of two products 96 and 97 (circa 3:1) in a good yield (75%). The product 97 was then isolated from the mixture using flash column chromatography in about 19% yield. Following this, dihydroxylation of 97 using OsO₄ gave the triol derivative 98 in a very good yield (80%). Removal of the Boc group on 98, under acidic conditions (TFA/DCM) furnished the desired amino triols, followed by cyclisation under Mitsunobu conditions, which afforded indolizidine derivative 99 in a 65% yield. Diacetylation on 99 was then performed to give 100 in a very good yield (85%). Finally, hydrolysis of acetyl and benzyl groups at 100 using H₂/PdCl₂ provided the desired natural product 1 in an 86% {7% overall yield from the intermediate 93 (Scheme 9)}.

Scheme 9: Stereoselective total synthesis of natural product (-)-swainsonine 1 by Singh, Manna and Panda

Another asymmetric synthesis of (-)-swainsonine 1 has been reported by Yu and co-workers,⁸¹ which includes using nitrone 101 as a key intermediate in the synthetic route (Scheme 10). The product 101 was synthesised in a 43% overall yield from D-mannose using literature procedures.^82,83The epimerisation of stereochemistry of C-5 at 101 was achieved successfully over a sequence of three steps. Reduction of 101 with NaBH₄ afforded hydroxyl amine 102 in 89% yield, followed by regioselective oxidation with MnO₂, which gave a mixture of 103 and 104 (around 3:1) in an excellent yield (95%). The desired regioisomer 103 was then reduced with NaBH₄ to provide N-hydroxypyrrolidine derivative 105 as a single diastereoisomer in 94% yield. Following this, reduction of 105 with Zn/Cu(OAc)₂ gave an amine derivative 106, which was then directly protected with CbzCl in a one-pot reaction to afford 107 in a very good yield (89%). Thereafter, acetonide group at 107 was cleaved using H₂SO₄-MeOH, which provided the desired diol 109 in 52% yield with the undesired tetrahydroxylated pyrrolidine product 108 in only 6.5% yield. The primary hydroxyl group at 109 was protected with TBSCl, followed by protection of the secondary hydroxyl group with MOMCl in a one-pot reaction to furnish 110 in a good yield (76%). Deprotection of TBS group at 110 afforded a primary alcohol 111 in an excellent yield (91%), which was done using Olah’s reagent {(pyridinium poly (hydrogen fluoride)}.^84,85 The alcohol 111 was then oxidised with a Dess-Martin reagent to give the corresponding aldehyde, and a subsequent Wittig reaction with methyl 2-(triphenylphosphoranylidene) acetate 112 in a one-pot reaction gave 113. Hydrogenation and cyclisation of the crude material of 113 provided δ-lactam 114 in a 79% overall yield. Next, reduction of 114 with LiAlH₄ afforded the corresponding tertiary amine 115, which was followed by removal of acetonide and MOM protecting groups using acidic conditions (HCl 3.0 N, MeOH) to give the desired (-)-swainsonine 1 in a good yield (74% from 115) (Scheme 10).

Scheme 10: Asymmetric synthesis of (-)-swainsonine 1 by Yu and co-workers

REFERENCES:

1. Kurgat CC, Kibet JK, Cheplogoi PK, Limo SC, Kimani PM. Asian Journal of Research in Chemistry, 2016; 11, 205.

2. Mumu C. Asian Journal of Research in Chemistry, 2018; 11, 337.

3. Premlata S, Krishan KM, Padma K. Asian Journal of Research in Chemistry, 2018; 11, 432.

4. Muthumani P, Meera R, Devi P, Kameswari B. Research Journal of Pharmacy and Technology, 2010; 3, 736.

5. Dheeraj A, Bharti A, Anish C. Research Journal of Pharmacy and Technology, 2013; 6, 618.

6. Shanaz B, Josephine LJ, Manjula D, Premakumari KB. Research Journal of Pharmacy and Technology, 2020; 13, 163.

7. Fowsiya J, Madhumitha G. Research Journal of Pharmacy and Technology, 2020; 13, 963.

8. Monago CC, Nwodo O, Fred C. Research Journal of Pharmacognosy and Phytochemistry, 2010; 2, 331.

9. Shukla A, Bigoniya P. Research Journal of Pharmacognosy and Phytochemistry, 2013; 5, 94.

10. AL-Khateeb IH. Baghdad Science Journal, 2019, 16, 550-554.

11. Demelo EB, Silveria GA, Carvalho I. Tetrahedron, 2006;62, 10277.

12. Lillelund VH, Jensen HH, Liang XF, Bols M. Chemical Review,2002; 102, 515.

13. Heihtman TD, Vasella AT. Angewandte Chemie International Edition,1999; 38, 750.

14. Asano N, Nash RJ, Molyneux RJ, Fleet GWJ. Tetrahedron Asymmetry,2000;11, 1645.

15. Asano N. Glycobiology,2003, 13, 93R.

16. Watson A, Fleet GWJ, AsanoN, Molyneux RJ, Nash RJ. Phytochemistry,2001;56, 265.

17. Gerber LS, Juillerat JL. Mini-Reviews in Medicinal Chemistry,2006;6, 1043.

18. MichaelJP. Natural Product Reports, 2004; 19, 625.

19. Asano N, Nash RJ, Molyneux RJ, Fleet GWJ. Tetrahedron Asymmetry, 2000; 11,1645.

20. Guengerich FP, Di Mari SJ, Broquist HP. Journal of the American Chemical Society, 1973;95, 2055.

21. Colegate SM, Dorling PR, Huxtable CR. Australian Journal of Chemistry,1979;32, 2257.

22. Marilyn JS, Frank SU, Harry PB, Thomas MH. Tetrahedron, 1983;39,29.

23. Hino M, Nakayama O, Tsurumi Y, Adachi K, Shibata T, Terano H, Kohsaka M, Aoki H, Imanaka H. The Journal of Antibiotics, 1985; 38, 926.

24. Patrick M, Adlard MW, Keshavarz T. Biotechnology Letters, 1993; 15, 997e1000.

25. Molyneux RJ, James LF. Science, Washington, D.C.1982; 216, 190.

26. Davis D, Schwarz P, Hernandez T, Mitchell M, Warnock B, Elbein AD. Plant Physiology, 1984; 76, 972.

27. Elbein AD, Solf R, Dorling PR, Vosbeck K. Proceedings of the National Academy of Sciences, U.S.A., 1981; 78, 7393.

28. Kaushal GP, Szumilo T, Pastuszak I, Elbein AD. Biochemistry, 1990; 29, 2168.

29. Pastuszak I, Kaushal GP, Wall KA, Pan YT, Sturm A, Elbein AD. Glycobiology, 1990; 1, 71.

30. Schneider MJ, Ungemach FS, Broquist HP, Harris TM, Tetrahedron, 1983; 39, 29.

31. Liao YF, Lal A, Moremen KW. The Journal of Biological Chemistry, 1996; 271, 28348.

32. Burgess K, HendersonI. Tetrahedron,1992;48, 4045.

33. Goss PE, Reid CL, Bailey D, Dennis JW. Clinical Cancer Research,1997;3, 11077.

34. Galustian C, Foulds S, Dye JF, Guillou PJ. Immunopharmacology, 1994;27, 165.

35. Granato DA, Neeser JR. Molecular Immunology, 1987; 24, 849.

36. Humphries MJ, Matsumoto K, White SL, Molyneus RJ, Olden K. Cancer Research, 1988; 48, 1410.

37. Elbein AD, Dorling PR, Vosbeck K, Horisberger M. The journal of Biological Chemistry,1982; 257, 1573.

38. Bowen D, Southerland WM, Bowen CD, Hughes DE. Anticancer Research, 1997; 17, 4345.

39. White SL. NagaiT, Akiyama SK, Reeves EJ, Grzegorzewski K, Olden K. Cancer Communications, 1991; 3, 83.

40. Dennis JW, Koch K, Beckner D. The Journal of the National Cancer Institute, 1989; 81, 1028.

41. Dennis JW. Cancer Research, 1986; 46, 5131.

42. Chao Li, Peipei Wang, Ziyang Fu, Yongtao Li, Shouju Li. Artificial Cells, Nanomedicine, and Biotechnology, 2019; 47, 2256.

43. Yagita M, Noda I, Maehara M, Fujieda S, Inoue Y, Hoshino T, Saksela E. The International Journal of Cancer, 1992; 52, 664.

44. Klein JLD, Roberts JD, George MD, Kurtzberg J, Breton P, Chermann JC, OldenK. British Journal of Cancer, 1999; 80, 87.

45. Skelton BW, White AH. Australian Journal of Chemistry, 1980; 33, 435.

46. Schneider MJ, Ungemach FS, Broquist HP, Harris TM. The Journal of the American Chemical Society, 1982; 104, 6863.

47. Kardono LBS, Kinghorn AD, Molyneux RJ. Phytochemical Analysis, 1991; 2, 120.

48. Schneider MJ, Ungemach FS, Broquist HP and Harris TM. Tetrahedron, 1983; 2, 29.

49. Gross PE, Baker MA, Carver JP, Dennis JW. Clinical Cancer Research,1995;1, 935.

50. Wikler DA, Holan G. The Journal of Medicinal Chemistry,1989;32, 2084.

51. Anzeveno PB, Creemer LJ, Daniel JK, King CH, Liu PS. The Journal of Organic Chemistry,1989;54, 2539.

52. Ahmed El Nemr. Tetrahedron, 56, 2000; 8579.

53. S. G. Pyne. Current Organic Synthesis, 2005; 2, 39-57.

54. Martίn R, Murruzzu C, Pericás MA, Riera A. The Journal of Organic Chemistry,2005; 70, 2325.

55. Gao Y, Hanson RM, Klunder JM, Ko SY, Masamune H, Sharpless KB. The Journal of the American Chemical Society,1987; 109, 5765.

56. Katsuki T, Martίn VS. Organic Reactions,1996; 48, 1-299.

57. Bernet B, Vasella A. Tetrahedron Letters,1983; 24, 5491.

58. Li YL, Wu YL. Tetrahedron Letters,1995; 36, 3875.

59. Still WC, Gennari C. Tetrahedron Letters, 1983; 24, 4405.

60. Guo H., O’Doherty GA. Organic Letters, 2006; 8, 1609.

61. Li M, Scott JG, O’Doherty GA. Tetrahedron Letters, 2004; 45, 1005.

62. Ceccon J, Greene AE, Poisson JF. Organic Letters, 2006; 8, 4739.

63. Denmark SE, Dixon JA. The Journal of Organic Chemistry,1998; 63, 6178.

64. Shi GF, Li JQ, Jiang XP, Cheng Y. Tetrahedron, 2008; 64, 5005.

65. Buchanan JG, Jigajinni VB, Singh G, Wightman RH. J. Chem. Soc., Perkin Trans. 1, 1987; 2377.

66. Buchanan JG, Singh G, Wightman RH. J. Chem. Soc., Chem. Commun., 1984; 1299.

67. Jiang XP, Cheng Y, Shi GF, Kang ZM. The Journal of Organic Chemistry, 2007; 72, 2212.

68. Sharma PK, Shah RN, Carver JP. Organic Process Research and Development, 2008;12, 831.

69. Tian YS, Joo JE, Kong BS, Pham VT, Lee KY, Ham WH. The Journal of Organic Chemistry,2009; 74, 3962.

70. Pyun SJ, Lee KY, Oh CY, Ham WH. Heterocycles,2004;62, 333.

71. Wardrop DJ, Bowen EG. Organic Letters, 2011; 13, 2376.

72. Cohen N, Banner BL, Laurenzano AJ, Carozza L. In Organic Syntheses; Wiley and Sons: New York, 1990; Vol. IV, pp 432-435.

73. Dunigan J, Weigel, LO. The Journal of Organic Chemistry, 1991; 56, 6225.

74. Li QR, Dong GR, Park SJ, Hong YR, Kim IS, Jung YH. European Journal of Organic Chemistry,2013; 4427.

75. Marshall JA, Seletsky BM, Luke GP. The Journal of Organic Chemistry,1994; 59, 3413.

76. Martinez PG, Dessolin M, Guibé F, Albericio F.J. Chem. Soc. Perkin Trans. 1,1999; 2871.

77. Au CWG, Pyne SG. The Journal of Organic Chemistry,2006;71, 7097.

78. Singh P, Manna SK, Panda G. Tetrahedron, 2014; 70 1363.

79. Garner P, Park JM. The Journal of Organic Chemistry, 1988; 53, 2979.

80. Srivastava AK, Das SK, Panda G. Tetrahedron, 2009; 65, 5322.

81. Qian BC, Kamori A, Kinami K, Kato A, Li YX, Fleet GWJ, Yu CY. Organic and Biomolecular Chemistry, 2016; 14, 4488.

82. Wang WB, Huang MH, Li YX, Rui PX, Hu XG, Zhang W, Su JK, Zhang ZL, Zhu JS, Xu WH, Xie XQ, Jia YM, Yu CY. Synlett, 2010; 488.

83. Tamura O, Toyao A, Ishibashi H. Synlett., 2002; 1344.

84. Nicolaou KC, Seitz SP, Pavia MR, Petasis NA. The Journal of Organic Chemistry, 1979; 44, 4011.

85. Masamune S, Lu LDL, Jackson WP, Kaiho T, Toyoda T. J. Am. Chem. Soc., 1982; 104, 5523.

Received on 18.01.2020 Modified on 21.03.2020

Research J. Pharm. and Tech. 2021; 14(1):531-537.

DOI: 10.5958/0974-360X.2021.00097.4