A theoretical study to elucidate the mechanistic aspects involved in the tosylation-cyclization reaction of diastereomeric phytosphingosines 1a-1d to jaspines 4a-4d is presented. The stereochemistry of the starting stereoisomers is crucial for the development of weak interactions, both in the reactants and in the transition states. The analysis of the energy barriers of each elementary reaction is consistent with the observed reluctance of tosylate 2d to undergo cyclization. In addition, the initial tosylation can be identified as the limiting step in cyclizations from 1a and 1b.
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2.
For recent synthetic approaches to jaspine B, and analogs, see: (a) DhandV., ChangS., BrittonR. (2013) Synthesis of pachastrissamine (jaspine B) and its derivatives by the late-stage introduction of the C-2 alkyl side-chains using olefin cross metathesis. Journal of Organic Chemistry, 78, 8208–8213; (b) Ghosal P, Ajay S, Meena S, Sinha S, Shaw AK. (2013) Stereoselective total synthesis of Jaspine B (Pachastrissamine) utilizing iodocyclization and an investigation of its cytotoxic activity. Tetrahedron: Asymmetry, 24, 903–908; (c) Jana AK, Panda G. (2013) Stereoselective synthesis of Jaspine B and its C2 epimer from Garner aldehyde. Royal Society of Chemistry Advances, 3, 16795–16801; (d) Martinkova M, Pomikalova K, Gonda J, Vilkova M. (2013) A common approach to the total synthesis of L-arabino-, L-ribo-C18-phytosphingosines, ent-2-epi-jaspine B and 3-epi-jaspine B from D-mannose. Tetrahedron, 69, 8228–8244; (e) Santos C, Fabing I, Saffon N, Ballereau S, Genisson Y. (2013) Rapid access to jaspine B and its enantiomer. Tetrahedron, 69, 7227–7233; (f) Yoshimitsu Y, Miyagaki J, Oishi S, Fujii N, Ohno H. (2013) Synthesis of pachastrissamine (jaspine B) and its derivatives by the late-stage introduction of the C-2 alkyl side-chains using olefin cross metathesis. Tetrahedron, 69, 4211–4220; (g) Srinivas Rao G, Chandrasekhar B, Venkateswara Rao B. (2012) Total synthesis of the acetyl derivatives of lyxo-(2R,3R,4R)-phytosphingosine and (-)-jaspine B. Tetrahedron: Asymmetry, 23, 564–569; (h) Zhao M-L, Zhang E, Gao J, Zhang Z, Zhao Y-T, Qu W, Liu H-M. (2012) An efficient and convenient formal synthesis of Jaspine B from D-xylose. Carbohydrate Research351, 126–129.
3.
DelgadoA., FabriàsG., CasasJ., AbadJ.L. (2013) Natural products as platforms for the design of sphingolipid-related anticancer agents. Advances in Cancer Research, 117, 237–281.
4.
CanalsD., MormeneoD., FabriàsG., LlebariaA., CasasJ., DelgadoA. (2009) Synthesis and biological properties of pachastrissamine (jaspine B) and diastereoisomeric jaspines. Bioorganic and. Medicinal Chemistry, 17, 235–241.
5.
Van den BergR.J., BoltjeT.J., VerhagenC.P., LitjensR.E., van der MarelG.A., OverkleeftH.S. (2006) An efficient synthesis of the natural tetrahydrofuran pachastrissamine starting from D-ribo-phytosphingosine. Journal of. Organic Chemistry71, 836–839.
6.
Compound 5 was obtained in 13% yield. Formation of 5 can be interpreted as a result of an intramolecular displacement of the tosyloxy group in 2d by the carbonyl group of the carbamate moiety.
Torrent-SucarratM., AngladaJ.M. (2006) On the gas phase hydrogen bond complexes between formic acid and hydroperoxyl radical. A theoretical study. Journal of Physical Chemistry A, 110, 9718–9726.
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