Tetrahedron Letters 52 (2011) 3942–3944
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A stereo-divergent route to aminocyclopentitol derivatives Shital K. Chattopadhyay ⇑, Ayan Bandyopadhyay Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
a r t i c l e
i n f o
Article history: Received 29 April 2011 Revised 20 May 2011 Accepted 22 May 2011 Available online 30 May 2011
a b s t r a c t A stereo-divergent synthetic strategy based on diastereoselective vinylation of an a-amino aldehyde, ring-closing metathesis reaction and diastereoselective dihydroxylation reaction as key steps has been developed for the synthesis of three aminocyclopentitol derivatives of chemical and biological relevance. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Cyclopentitol Asymmetric synthesis Amino acids Ring-closing metathesis
Aminocyclopentitol structures are present in a number of natural products such as mannostatin1 (1) and trehazolin2 (2, Fig. 1) which display high activity in glycosidase inhibition, a property relevant to the treatment of myriad diseases like type 2 diabetes mellitus, metastatic cancer, viral and bacterial infections like neuraminidase activity and human innunodeficiency.3 Inspired by these lead compounds, a library of aminocyclopentitol derivatives have been prepared and evaluated.4 These studies have revealed that regio- and streochemical diversities within the cyclic framework may subtly influence their biological activity, and sometimes a desired potency is achieved through structural manipulation based on mechanistic studies.5 Synthetic entry to this pharmaceutically important scaffold, therefore, continues to be reported.6 However, development of common synthetic route to various stereoisomeric cyclopentitol derivatives remains important. Herein, we wish to report a simple entry to a few such derivatives from L-serine. Our synthesis started from the known7 Garner’s aldehydederived allyl alcohol 3 (Scheme 1) which was protected as its tertbutyldiphenylsilyl (TBDPS) ether 4. The oxazolidine ring in compound 4 was then opened with acid to provide the amino alcohol 5 which was quickly oxidised with Dess–Martin periodinane8 following precedence.9 The aldehyde 6, [a]D 53.3 (c 1.35, CHCl3), proved to be essentially pure and could be stored, if necessary, at 20 °C for 7 days without appreciable racemisation as judged from repeated spectroscopic and optical measurement experiments. For practical purpose, it was used as such in the next step. Addition of vinylmagnesium bromide to this aldehyde then gave a separable mixture of the allyl alcohols 7 and 8 in the ratio of 7:3. The major isomer was
⇑ Corresponding author. Fax: +91 33 25828282. E-mail address:
[email protected] (S.K. Chattopadhyay). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.05.103
HO
OH
HO
HO
SMe
OH
HO
NH2
N O
1, Mannostatin A
OH
NHR
2, Trehazolin
Figure 1.
assigned syn-configuration based on the assumption that chelation control10 had prevailed and with further support from the following synthetic work. Thus, the diene 7 was subjected to undergo ring-closure with Grubbs’ first generation catalyst benzylidene bistricyclohexyl phosphinoruthenium(IV) dichloride11 9 to obtain the corresponding cyclopentene 10 in good yield. Deprotection of the TBDPS group from 10 then led to the dihydroxy derivative 11, [a]D 33.0 (c 0.52, CHCl3). An identical sequence of reactions on the minor diene 8 provided the isomeric diol 13. Comparison of 1H and 13C NMR spectra of each of the diols 11 and 13 quickly revealed the symmetry present in 13 and hence the configuration of the new stereocentre in 7 and 8. Similarly, starting from the known allyl alcohol 14 (Scheme 2), the chiral a-amino aldehyde 17, [a]D 46.1 (c 1.25, CHCl3), was prepared in an overall yield of 66% over three convenient steps. Compound 17 too proved to be isolable and stable enough for characterisation and it could be stored also at 20 °C for a week. Addition of vinylmagnesium bromide to 17 proceeded to deliver the allyl alcohol 18 as a single isolable product and in distereomerically pure form as judged from its spectroscopic and chromatographic
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S. K. Chattopadhyay, A. Bandyopadhyay / Tetrahedron Letters 52 (2011) 3942–3944
OR O
OTBDPS ii
HO BocHN
NBoc
3, R = H 4, R = TBDPS
O
i or ii
10
iv BocHN
OTBDPS
OTBDPS
OH
12
7
HO
HO
vi OTBDPS NHBoc
HO
8
v
HO
HO 19
11
vi OTBDPS NHBoc
HO
HO
HO
NHBoc
OTBDPS NHBoc
HO
(HPLC) behaviour. The configuration of the new stereocentre in 18 was similarly assigned as syn and was also corroborated by its conversion to the meso-diol 20 through the two-step sequence outlined above, that is, ring-closing metathesis (RCM) leading to 19 and then deprotection of the TBDPS group. Having access to the stereo-defined aminocyclopentene derivatives 10, 12 and 19, we focussed on their conversion to the targeted aminocyclopentitol derivatives through a possible diastereoselective dihydroxylation reaction of the double bond present in these structures Thus, dihydroxylation of 10 (Scheme 3) under Upjohn conditions12 led to the formation of a single diastereomer in 96% yield which was assigned configuration based on the assumption that dihydroxylation has taken place opposite to the bulky OTBDPS group. Dihydoxylation under hydroxy directed conditions as reported by Donohoe et al.13 also produced the same stereoisomer, as expected, albeit in lower yields. Deprotection of the TBDPS group from 21 then smoothly led to the aminocyclipentitol derivative 22 in very good yield. Similarly, dihydroxylation of the cyclopentene derivative 12 under analogous conditions led to the formation of a single diastereomer whose stereochemistry was assigned as in 23 based on the belief that dihydroxylation has taken place from the side opposite to the adjacent bulky groups. Deprotection of OR
HO
14, R = H
OTBDPS NHBoc 26
OH
OH NHBoc 27
the TBDPS group from 23 then led to the meso-aminocyclopentitol derivative 24. The cyclopentene derivative 19 also showed very similar behaviour during dihydroxylation providing 25 as the only product in an overall yield of 41% over six steps. The latter, on treatment with 2,2-dimethoxypropane in the presence of a catalytic amount of p-TSA provided a single acetonide 26 in near quantitative yield. Deprotection of the TBDPS group from 25 then provided the meso-diol 27. This information, that is, formation of a single acetonide from 25, and symmetric nature of the diol 27 helped us to assign the stereochemistry of the triol 25 as depicted. In conclusion, we have developed a short and efficient synthetic protocol involving stereoselective vinylation of a a-chiral aldehyde leading to three stereo-defined aminocyclopentene-1,3-diol derivatives viz. 10, 12 and 19 which may be considered as important building blocks based on similar applications.14 Dihydroxylation of each of these three cyclopentene derivatives was found to be extremely facile and highly stereoselective providing access15 to the triols 21, 23 and 25 which may also be considered as useful building blocks in the design and synthesis of aminocyclopentitol
OTBDPS
O iii
HO BocHN
NBoc
HO
Scheme 3. Reagents and conditions: (i) OsO4 (5 mol%), N-methylmorpholine-Noxide (NMMO) (2 equiv), acetone–water (5:1), 24 h, 96% for 21; 94% for 23; 97% for 25; (ii) OsO4 (5 mol %), EDTA, CH2Cl2, 24 h, 81%; (iii) n-Bu4N+F , THF, rt, 4 h, 89% for 22, 87% for 24, 97% for 27; (iv) 2,2-dimethoxypropane, p-TsOH, CH2Cl2, rt, 0.5 h, 96%.
OTBDPS ii
O
iii
25
Scheme 1. Reagents and conditions: (i) TBDPSCl, imidazole, CH2Cl2, rt, 3 h, 98%; (ii) p-TsOH (0.3 equiv), MeOH, rt, 2 h, 80%; (iii) Dess–Martin periodinane, CH2Cl2, rt, 0.5 h, 94%; (iv) vinylmagnesium bromide, 78 to 20 °C, 3 h, 72%; (v) 9 (5 mol %), CH2Cl2 (0.01 M), rt, 12 h, 85% for 10, 79% for 12; (vi) n-Bu4N+F , THF, rt, 4 h, 93% for 11, 89% for 13.
OH NHBoc
iv
25
13
OH
24
O
OH
i
OH
12
O
HO
OH
OH NHBoc
10
22
OTBDPS NHBoc 23
8
v
OH NHBoc
iii
BocHN
7
HO
OTBDPS NHBoc 21
i
+ BocHN
OH
iii HO
HO
OH
HO
OH
6
5
i
HO
OTBDPS
iii
iv BocHN 17
16 i
15, R = TBDPS OH
BocHN 18
OTBDPS v
HO
vi OTBDPS NHBoc 19
HO
OH NHBoc 20
Scheme 2. Reagents and conditions: (i) TBDPSCl, imidazole, CH2Cl2, rt, 3 h, 93%; (ii) p-TsOH (0.3 equiv), MeOH, rt, 3 h, 77%; (iii) Dess–Martin periodinane, CH2Cl2, rt, 0.5 h, 92%; (iv) vinylmagnesium bromide, 78 to 20 °C, 3 h, 74%; (v) 9 (5 mol %), CH2Cl2 (0.01 M), rt, 12 h, 86%; (vi) n-Bu4N+F , THF, rt, 4 h, 95%.
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derivatives of interest. Ease of availability of starting materials, use of less expensive reagents, high yields in most of the conversions, useful level of stereoselectivity, pre-determined mode of ring-closure, divergence and diversity in the stereochemical pattern are some of the attractive features of our protocol which may complement to those existing in the literature for the preparation of such types of compounds. Acknowledgements We are thankful to DST (Grant No. SR/S1-OC/35/2009), Government of India, for financial assistance and CSIR for fellowship to one of us (A.B.). References and notes 1. Aoyagi, T.; Yamamoto, T.; Kojiri, K.; Morishima, H.; Nagai, M.; Hamada, M.; Takeuchi, T.; Umezawa, H. J. Antibiot. 1989, 42, 883. 2. Kobayashi, Y.; Miyazaki, H.; Shiozaki, M. J. Am. Chem. 1992, 114, 10065. 3. (a) de Melo, E. B.; Gomes, A. S.; Carvalho, I. Tetrahedron 2006, 62, 10277; (b) Asano, N. Glycobiology 2003, 13, 93R; (c) Smith, B. J.; Mckimm-Breshkin, J. L.; McDonald, M.; Fernley, R. T.; Varghese, J. N.; Colman, P. M. J. Med. Chem. 2002, 45, 2207. 4. For some reviews, see: (a) Bereciber, A.; Grandjean, C.; Sriwardena, C. Chem. Rev. 1999, 99, 779; (b) Arjona, O.; Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107, 1919; (c) Deglado, A. Eur. J. Org. Chem. 2008, 23, 3893; (d) Ganem, B. Acc. Chem. Res. 1996, 29, 340; (e) Bols, M. Acc. Chem. Res. 1998, 31, 1. 5. (a) Dickson, L. G.; Leroy, E.; Reymond, J.-L. Org. Biomol. Chem. 2007, 5, 3164; (b) Bourne, Y.; Henrissat, B. Curr. Opin. Struct. Biol. 2001, 11, 593; (c) Compain, P.; Martin, O. R. Curr. Top. Med. Chem. 2003, 3, 541; (d) Blaser, A.; Reymond, J.-L. Org. Lett. 2000, 2, 1733; (e) Leroy, E.; Reymond, J.-L. Org. Lett. 1999, 1, 775; (f) Blaser, A.; Reymond, J.-L. Org. Lett. 2000, 2, 151. 6. For some assorted reports, see: (a) Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W. J. Tetrahedron: Asymmetry 2000, 11, 1645; (b) Blaser, A.; Reymond, J.-L. Synlett 2000, 817; (c) McAllister, G. D.; Taylor, R. J. K. Tetrahedron Lett. 2001, 42, 1197; (d) Mehta, G.; Mohal, N. Tetrahedron Lett. 2001, 42, 4227; (e) Soengas, R. G.; Estevez, J. C.; Estevez, R. J. Org. Lett. 2003, 5, 1423; (f) Kummeter, M.; Kazmaier, U. Eur. J. Org. Chem. 2003, 3325; (g) Chiara, J. L.; de Garcia, I. S.; Bastida, A. Chem. Commun. 2003, 1874; (h) Bojstrup, M.; Fanefjord, M.; Lundt, I. Org. Biomol. Chem. 2007, 5, 3164; (i) Kim, I. S.; Li, Q. R.; Lee, J. K.; Lee, S. H.; Lim, J. K.; Zee, O. P.; Jung, Y. H. Synlett 2007, 1711; (j) Chakraborty, C.; Vyavahare, V. P.; Puranik, V. G.; Dhavale, D. D. Tetrahedron 2008, 64, 9574; (k) Reddy, Y. S.; Kadigachalam, P.; Doddi, V. R.; Vankar, Y. D. Tetrahedron Lett. 2009, 50, 5827; (l) Rao, J. P.; Rao, B. V.; Swarnalatha, J. L. Tetrahedron Lett. 2010, 51, 3083. 7. (a) Garner, P.; Park, J. M. J. Org. Chem. 1988, 53, 2979; (b) Herold, P. Helv. Chim. Acta 1988, 71, 354; (c) Bandyopadhyay, A.; Pal, B. K.; Chattopadhyay, S. K. Tetrahedron: Asymmetry 2008, 19, 1875. 8. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155. 9. Cooke, J. W. B.; Davies, S. G.; Naylor, A. Tetrahedron 1993, 49, 7955. 10. (a) Denis, J.-N.; Correa, A.; Greene, A. E. J. Org. Chem. 1991, 56, 6939; (b) Ibuka, T.; Habashita, H.; Otaka, A.; Fujii, N.; Oguchi, Y.; Ueyhara, T.; Yamamoto, Y. J. Org. Chem. 1991, 56, 4370; (c) Sames, D.; Polt, R. J. Org. Chem. 1994, 59, 4596; (d) Ravikumar, J. S.; Dutta, A. Tetrahedron Lett. 1999, 40, 1381; (e) Chattopadhyay, S. K.; Roy, S. P. Tetrahedron Lett. 2008, 49, 5498.
11. (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 100; (b) Grubbs, R. H. Tetrahedron 2004, 60, 2117; For a recent review on the RCM of hetero atom-tethered dienes, see: (c) Chattopadhyay, S. K.; Karmakar, S.; Biswas, T.; Majumdar, K. C.; Rahaman, H.; Roy, B. Tetrahedron 2007, 63, 3919. 12. VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 17, 1973. 13. Donohoe, T. J.; Moore, P. R.; Waring, M. J. Tetrahedron Lett. 1997, 38, 5027. 14. (a) Lu, H.; Mariano, P. S.; Lam, Y.-F. Tetrahedron Lett. 2001, 42, 4755; (b) Cho, S. J.; Ling, R.; Kim, A.; Mariano, P. S. J. Org. Chem. 2000, 65, 1574; (c) Ling, R.; Mariano, P. S. J. Org. Chem. 1998, 63, 6072. 15. All new compounds reported gave satisfactory spectroscopic and/or analytical data. Compound 7: [a]D +21.8 (c 0.9, CHCl3), IR (CHCl3): 3445, 1715, 1501, 1170, 702 cm 1. 1H NMR (400 MHz, CDCl3): d 7.65–7.63 (m, 4H), 7.44–7.35 (6H, m), 5.85–5.68 (2H, m), 5.32–5.27 (1H, dd, J = 16.8, 1.6 Hz), 5.16–5.0 (4H, m), 4.60–4.48 (2H, m), 3.53–3.30 (2H, m), 1.38 (9H, s), 1.09 (9H, s). 13C NMR (125 MHz, CDCl3): 156.0, 137.4, 136.9, 136.0, 132.9, 132.6, 130.1, 129.9, 127.8, 127.6, 117.6, 116.0, 79.3, 77.5, 70.6, 57.9, 28.3, 27.1, 19.4. M.S (TOF MS ES+): 504 (M+Na). Anal. Calcd for C28H39NO4Si: C, 69.82; H, 8.16; N, 2.91. Found: C, 69.98; H, 8.28; N, 3.20. Compound 8: [a]D +7.3 (c 0.55, CHCl3). IR (CHCl3): 3444, 1705, 1505, 702 cm 1, 1 H NMR (400 MHz, CDCl3): d 7.73–7.62 (4H, m), 7.45–7.34 (6H, m), 5.9–5.82 (1H, m), 5.77–5.71 (1H, m), 5.25 (1H, d, J = 16.4 Hz), 5.18–5.05 (3H, m), 4.64 (1H, br s), 4.34–4.29 (2H, m), 3.75–3.64 (1H, m), 2.67 (1H, d, J = 6 Hz) 1.40 (9H, s), 1.07 (9H, s). 13C NMR (100 MHz, CDCl3): d 156.3, 137.3, 137.1, 136.0, 135.9, 133.4, 133.2, 130.0, 129.7, 127.7, 127.5, 117.5, 115.9, 79.5, 74.9, 72.8, 59.6, 28.3, 27.1, 19.4. MS (TOF MS ES+): 504 (M+Na). Anal. Calcd for C28H39NO4Si: C, 69.82; H, 8.16; N, 2.91. Found: C, 70.06; H, 8.32; N, 3.25. Compound 18: [a]D 3.5 (c 0.84, CHCl3). IR (CHCl3): 3439, 1698, 1505, 1367, 1171, 1112, 702 cm 1. 1H NMR (400 MHz, CDCl3): d 7.68–7.63 (4H, m), 7.44– 7.34 (6H, m), 5.85–5.71 (2H, m), 5.23–5.10 (2H, m), 5.03–4.85 (3H, m), 4.45– 4.34 (2H, m), 3.62 (1H, br s), 2.47 (1H, br s), 1.42 (9H, s), 1.07 (9H, s). 13C NMR (100 MHz, CDCl3): d 155.4, 136.8, 136.5, 135.0, 134.9, 132.6, 132.1, 128.9, 128.7, 126.6, 126.4, 116.3, 115.1, 78.4, 74.5, 71.1, 57.8, 27.3, 26.0, 18.4. M.S (TOF MS ES+): 504 (M+Na). Anal. Calcd for C28H39NO4Si: C, 69.82; H, 8.16; N, 2.91. Found: C, 70.01; H, 8.29; N, 3.17. Compound 22: Mp: 96 °C. [a]D 39.9 (c 0.31, MeOH). IR (KBr): 3359, 1686, 1677, 1534, 1367, 1171 cm 1. 1H NMR (400 MHz, DMSO-d6): d 6.24 (d, 1H, J = 8.5 Hz), 4.70 (d, 1H, J = 5.6 Hz), 4.56 (1H, d, J = 6.0 Hz), 4.48 (1H, d, J = 6.4 Hz), 4.42 (1H, d, J = 4.4 Hz), 3.75–3.65 (4H, m), 3.57 (1H, q, J = 5.0 Hz), 1.38 (9H, s). 13C NMR (100 MHz, DMSO-d6): d 155.5, 77.4, 76.8, 73.9, 73.6, 70.1, 57.5, 28.3. HRMS (TOF MS ES+): obsd 272.1110 (M+Na); calcd 272.1110. Compound 24: Mp: 88 °C. IR (KBr): 3436, 1683, 1521, 1280, 1247, 1171, 1078 cm 1. 1H NMR (400 MHz, DMSO-d6): d 5.45 (1H, d, J = 9.2 Hz), 4.80 (2H, d, J = 4.8 Hz), 4.60 (2H, d, J = 3.2 Hz), 3.96 (1H, q, J = 6.4 Hz), 3.74–3.71 (4H, m), 1.38 (9H, s). 13C NMR (100 MHz, DMSO-d6): d 154.9, 77.7, 76.5, 74.6, 51.9, 28.2. HRM.S (TOF MS ES+): obsd 272.1113 (M+Na); calcd 272.1110. Compound 25: [a]D 6.9 (c 0.58, CHCl3). IR (CHCl3): 3404, 1694, 1515, 1392, 1366, 1169, 1112, 702 cm 1. 1H NMR (400 MHz, DMSO-d6): d 7.71–7.63 (4H, m), 7.45–7.35 (6H, m), 6.62 (1H, d, J = 9.2 Hz), 4.98 (1H, d, J = 6.0 Hz), 4.73 (1H, d, J = 5.2 Hz), 4.19 (1H, d, J = 4.0 Hz), 3.81 (1H, dd, J = 6.0, 2.4 Hz), 3.64–3.58 (3H, m), 3.54–3.50 (1H, m), 1.38 (9H, s), 1.10 (9H, s). 13C NMR (100 MHz, CDCl3): d 157.0, 135.8, 133.3, 133.1, 130.1, 128.0, 80.8, 80.3, 80.2, 76.2, 75.4, 63.9, 28.3, 26.9, 19.1. HRM.S (TOF MS ES+): obsd 510.2297 (M+Na); calcd 510.2288. Compound 27: Mp: 164–166 °C. IR (KBr): 3366, 1675, 1538, 1449, 1368, 1285, 1174, 1067 cm 1. 1H NMR (400 MHz, DMSO-d6): d 6.76 (1H, d, J = 8.4 Hz), 4.88 (d, 2H, J = 5.2 Hz), 4.53 (d, 2H, J = 3.2 Hz), 3.54–3.53 (m, 2H), 3.49–3.47 (m, 2H), 3.23 (q, 1H, J = 7.6 Hz), 1.38 (s, 9H). 13C NMR (100 MHz, DMSO-d6): d 155.8, 78.5, 77.4, 74.6, 61.0, 28.3. HRMS (TOF MS ES+): obsd 272.1111 (M+Na); calcd 272.1110.
