Proceedings book download - 5Z.com

tert-butylcarbonylation of the hydroxyl group and also of the sulfonamide function. Thus,the alternative reaction with 2 eq. of Boc 2 O was carried out [7]. In the case of reaction withcompounds 1b and 1c, the corresponding N-Nosyl, N-Boc-dehydroamino acid derivativeswere obtained (compounds 2b and 2c, 81% and 99% yield, respectively). In the case ofreaction with coupound 1a, the major product was the methyl ester of N-Boc, -(4-nitrophenylsulfinyl)- -dehydroserine [9]. The introduction of the tert-butyloxycarbonylgroup makes necessary a deprotection step prior to alkylation, so compounds 2b and 2cwere treated with a 4% solution of trifluoroacetic acid (Tfa) in dichloromethane to givecompounds 3b and 3c in high yields (84% and 83%, respectively). These N-Nosyldehydroaminoacid derivatives were subject to ethylation using the conditions proposed byLiguori [5] [2.5 eq. of Et 3 OBF 4 , 3.5 eq. of N,N-diisopropylethylamine (DIPEA) in drydichloromethane] to give the corresponding N-Nosyl, N-ethyldehydroamino acidderivatives in good yields (compounds 4b and 4c, 70% and 78%, respectively).In order to avoid the need for tert-butyloxycarbonyl group removal, an alternativestrategy in which alkylation occurs prior to dehydration was attempted (Route B,Scheme 1). Thus, compounds 1a-c were reacted directly without side chain protection with1 eq. of Et 3 OBF 4 . Fortunately, the reaction was regioselective giving the correspondingN-Nosyl, N-ethyl- -hydroxyamino acid derivative in high yields (compounds 5a-c, 92-94%). These could now be dehydrated by reaction with 1 eq. of Boc 2 O followed bytreatment with TMG. In the case of reaction with compounds 5a and 5c, good yields in thecorresponding N-Nosyl, N-ethyldehydroamino acid derivative were obtained (73% and62%, respectively). Attempts in dehydration of compound 5b resulted in long reactiontimes and complex mixtures which did not allow isolation of the product.In conclusion, the route in which alkylation occurs prior to dehydration results in onestep less, giving the N-ethyl derivatives of dehydroalanine and dehydrophenylalanine inoverall yields of 67% and 57%, respectively. The dehydrophenylalanine derivative and thecorresponding dehydroaminobutyric acid derivative could also be obtained by thealternative route (dehydration prior to alkylation) in overall yields of 64% and 48%,respectively. Thus, it was possible to obtain for the first time, new non-natural amino acidswhich incorporate both the N-alkyl and -dehydro moieties. These can be interestingprecursors of new peptides with potential pharmacological activity.AcknowledgmentsFoundation for Science and Technology (FCT) – Portugal and Fundo Europeu de DesenvolvimentoRegional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMRspectrometer Bruker Avance II + 400 is part of the National NMR Network and was purchased in theframework of the National Programme for Scientific Re-equipment, contract REDE/1517/RMN/2005,with funds from POCI 2010, FEDER and FCT.References1. Goodman, T., Moroder, L., In Houben-Weyl (Eds.) Synthesis of Peptides and Peptidomimetics,Thieme, Stuttgart, Germany, 2003, vol. E22c, p. 215-271.2. Aurelio, L., Brownlee, R.T.C., Hughes, A.B. Chem. Rev. 104, 5823-5846 (2004) and referencescited therein.3. Wenger, R.M. Angew. Chem., Int. Ed. Engl. 24, 77-85 (1985).4. Ruckle, T., Dubray, B., Hubler, F., Mutter, M. J. Pept. Sci. 5, 56-58 (1999).5. Belsito, E.L., De Marco, R., Di Gioia, M.L., Liguori, A., Perri, F., Viscomi, M.C. Eur. J. Org.Chem. 4245-4252 (2010).6. a) Palmer, D.E., Pattaroni, C., Nunami, K., Chadha, R.K., Goodman, M., Wakamiyia, T., Fukase,K., Horimoto, S., Kitazawa, M., Fujita, H., Kubo, A., Shiba, T. J. Am. Chem. Soc. 114, 5634-5642(1992); b) Jung, G. Angew. Chem., Int. Ed. Engl. 30, 1051-1068 (1991); c) Chatterjee, C., Paul, M.,Xie, L., Van Der Donk, W.A. Chem. Rev. 105, 633-684 (2005).7. Ferreira, P.M.T., Maia, H.L.S., Monteiro, L.S., Sacramento, J. J. Chem. Soc., Perkin Trans. 1 3697-3703 (1999).8. Ferreira, P.M.T., Monteiro, L.S., Pereira, G., Silva, L., Ribeiro, L., Sacramento, J. Eur. J. Org.Chem. 5934-5949 (2007).9. Ferreira, P.M.T., Maia, H.L.S., Monteiro, L.S. Eur. J. Org. Chem. 2635-2644 (2003).129