D
A. J. Brockway et al.
Paper
Synthesis
NaHCO3 (25 mL). The layers were separated and the organic layer was
dried (Na2SO4), filtered, and concentrated in vacuo to afford a clear
oil. The oil was purified by flash chromatography (silica gel, 0–10% 1%
NH4OH in CH3OH/100–90% CH2Cl2) to afford the product carbamate 4
as a white foam; yield: 1.87 g (61%); [α]D +5.0 (c 0.7, CHCl3).
References
(1) Pegg, A. E.; Casero, R. A. Jr. Meth. Mol. Biol. 2011, 720, 3.
(2) Pegg, A. E. Essays Biochem. 2009, 46, 25.
(3) Pegg, A. E. IUBMB Life 2009, 61, 880.
(4) Casero, R. A.; Pegg, A. E. Biochem. J. 2009, 421, 323.
(5) Dever, T. E.; Gutierrez, E.; Shin, B.-S. Crit. Rev. Biochem. Mol. Biol.
2014, 49, 413.
(6) Park, M. H.; Nishimura, K.; Zanelli, C. F.; Valentini, S. R. Amino
Acids 2010, 38, 491.
(7) Willert, E.; Phillips, M. A. Trends Parasitol. 2012, 28, 66.
(8) Kennedy, P. G. Lancet Neurol. 2013, 12, 186.
(9) Willert, E. K.; Fitzpatrick, R.; Phillips, M. A. Proc. Natl. Acad. Sci.
U.S.A. 2007, 104, 8275.
IR (thin film): 3325, 3176, 2927, 1699, 1646 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 8.34 (s, 1 H), 8.01 (br s, 1 H), 6.08 (br s,
1 H), 5.83 (br s, 2 H), 5.54–5.44 (m, 3 H), 5.06 (br s, 1 H), 4.92 (br s, 1
H), 4.41 (br s, 1 H), 3.76–3.61 (m, 2 H), 3.14–2.86 (m, 2 H), 2.59–2.49
(m, 2 H), 2.27 (s, 3 H), 1.61 (s, 3 H), 1.44 (s, 9 H), 1.39 (s, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 155.8, 155.5, 153.1, 149.3, 140.1,
129.5, 128.8, 120.3, 114.3, 91.1, 85.1, 84.1, 83.3, 79.3, 58.8, 54.5, 42.6,
37.6, 28.4, 27.0, 25.3.
(10) Casara, P.; Marchal, P.; Wagner, J.; Danzin, C. J. Am. Chem. Soc.
1989, 111, 9111.
LC/MS (ESI): m/z [M + H]+ calcd for C23H36N7O5: 490.3; found: 490.3.
(11) Bitonti, A. J.; Byers, T. L.; Bush, T. L.; Casara, P. J.; Bacchi, C. J.;
Clarkson, A. B. Jr.; McCann, P. P.; Sjoerdsma, A. Antimicrob.
Agents Chemother. 1990, 34, 1485.
(12) Bacchi, C. J.; Nathan, H. C.; Yarlett, N.; Goldberg, B.; McCann, P.
P.; Bitonti, A. J.; Sjoerdsma, A. Antimicrob. Agents Chemother.
1992, 36, 2736.
(13) Barker, R. H. Jr.; Liu, H.; Hirth, B.; Celatka, C. A.; Fitzpatrick, R.;
Xiang, Y.; Willert, E. K.; Phillips, M. A.; Kaiser, M.; Bacchi, C. J.;
Rodriguez, A.; Yarlett, N.; Klinger, J. D.; Sybertz, E. Antimicrob.
Agents Chemother. 2009, 53, 2052.
(14) Yu, W.; Chory, E. J.; Wernimont, A. K.; Tempel, W.; Scopton, A.;
Federation, A.; Marineau, J. J.; Qi, J.; Barsyte-Lovejoy, D.; Yi, J.;
Marcellus, R.; Iacob, R. E.; Engen, J. R.; Griffin, C.; Aman, A.;
Wienholds, E.; Li, F.; Pineda, J.; Estiu, G.; Shatseva, T.; Hajian, T.;
Al-awar, R.; Dick, J. E.; Vedadi, M.; Brown, P. J.; Arrowsmith, C.
H.; Bradner, J. E.; Schapira, M. Nat. Commun. 2012, 3, 1288; Cor-
rigendum: Nat. Commun. 2013, 4, 1893.
5′-{[(Z)-4-Aminobut-2-en-1-yl]methylamino}-5′-deoxyadenosine
(MDL 73811) (1)
To a stirred solution of carbamate 4 (1.25 g, 2.55 mmol) in CH3OH (15
mL) was added 1 M aq H2SO4 (15 mL). The resulting solution was
stirred at r.t. for 18 h before being concentrated in vacuo. The solution
was basified to pH >9 with 20% aq NaOH and concentrated in vacuo.
To the residual solid was added t-BuOH (15 mL) and the solution was
dried (Na2SO4), filtered, and concentrated in vacuo to afford a clear
oil. The oil was purified by flash chromatography (silica gel, 0–40% 1%
NH4OH in CH3OH/100–60% CH2Cl2) to afford the product amine 1 as a
white solid; yield: 0.53 g (60 %); mp 260 °C (dec.) [Lit.23 mp 260 °C
(dec.)].
IR (thin film): 3281, 2939, 1624, 1578 cm–1
.
1H NMR (CD3OD, 400 MHz): δ = 8.26 (s, 1 H), 8.19 (s, 1 H), 5.98 (d, J =
4.4 Hz, 1 H), 5.64–5.42 (m, 2 H), 4.71 (m, 1 H), 4.31–4.11 (m, 2 H),
3.72–3.64 (m, 2 H), 3.17 (d, J = 6.7 Hz, 2 H), 2.81 (d, J = 5.7 Hz, 2 H),
2.31 (s, 3 H).
1H NMR was in accordance with literature values.10
13C NMR (CDCl3, 100 MHz): δ = 157.3, 153.9, 150.5, 141.5, 131.6,
(15) Davis, M.; Dudman, N. P. B.; White, H. F. Aust. J. Chem. 1983, 36,
1623.
(16) Marasco, C. J. Jr.; Kramer, D. L.; Miller, J.; Porter, C. W.; Bacchi, C.
J.; Rattendi, D.; Kucera, L.; Iyer, N.; Bernacki, R.; Pera, P.; Sufrin,
J. R. J. Med. Chem. 2002, 45, 5112.
128.6, 120.6, 90.8, 83.3, 74.7, 73.7, 60.4, 55.3, 43.1, 38.4.
(17) Minnick, A. A.; Kenyon, G. L. J. Org. Chem. 1988, 53, 4952.
(18) Hirth, B.; Barker, R. H. Jr.; Celatka, C. A.; Klinger, J. D.; Liu, H.;
Nare, B.; Nijjar, A.; Phillips, M. A.; Sybertz, E.; Willert, E. K.;
Xiang, Y. Bioorg. Med. Chem. Lett. 2009, 19, 2916.
(19) NMR analysis indicated complete decomposition after storing a
freshly prepared sample of tert-butyl (Z)-[4-(methylamino)but-
2-en-1-yl]carbamate (5) in a capped vial at r.t. for 48 h.
(20) Joce, C.; Caryl, J.; Stockley, P. G.; Warriner, S.; Nelson, A. Org.
Biomol. Chem. 2009, 7, 635.
(21) Gray, N. S.; Zhou, W. (Gatekeeper Pharmaceuticals, Inc., USA)
WO2011140338 A1, 2011.
(22) Skerlj, R. T.; Bridger, G. J.; Kaller, A.; McEachern, E. J.; Crawford,
J. B.; Zhou, Y.; Atsma, B.; Langille, J.; Nan, S.; Veale, D.; Wilson,
T.; Harwig, C.; Hatse, S.; Princen, K.; De Clercq, E.; Schols, D.
J. Med. Chem. 2010, 53, 3376.
LC/MS (ESI): m/z [M + H]+ calcd for C15H24N7O3: 350.2; found: 350.2.
Acknowledgment
The authors acknowledge Jack Hunt for synthetic contributions to
this project. This work was supported by funds from the National In-
stitutes of Health grant R01AI090599 (to M.A.P. and J.K.D.B.). M.A.P.
and J.K.D.B. acknowledge the support of the Welch Foundation
(grants I-1257 and I-1422, respectively). M.A.P. holds the Beatrice and
Miguel Elias Distinguished Chair in Biomedical Science and the Caro-
lyn R. Bacon Professorship in Medical Science and Education. J.K.D.B.
holds the Julie and Louis Beecherl, Jr., Chair in Medical Science.
(23) Casara, P.; Danzin, C. (Merrell Dow Pharmaceuticals, Inc., USA)
EP 0358536 A2, 1990.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–D