Batzelladine alkaloids

Six-membered cyclic guanidine 197 was transformed into the corresponding bicyclic guanidine hemiaminal after deprotection of the Cbz and contemporary cyclization on the masked aldehyde function (Equation 4). This product, 198, was then employed in a Biginelli reaction to form a precursor of alkaloid batzelladine F <1999JOC1512>. 

Other procedures using TPAP/NMO/PMS/CH Cl include steps in the synthesis of (+)-altholactone (lactol to lactone) [78] antheliolide A [168] the AChE inhibitor (+)-arisugacin A and B (primary alcohol to aldehyde step also) [83] the marine macrolide amphidinolide T1 [169] the alkaloid (+)-batzelladine D cf. mech. 

Rao, A.V.R., Gurjar, M.K., and Vasudevan, J. (1995) An enantiospecific synthesis of the tricychc guanidine segment of the anti-HIV marine alkaloid batzelladine A. J. Chem. Soc. Chem. Common., 1369-1370. 

Evans, PA., Qin, (., Robinson, J.E., and Bazin, B. (2007) Enatioselective total synthesis of the polycyclic guanidine-containing marine alkaloid (—)-batzelladine D. Angew. Chem. Int. Ed., 46, 7417-7419. 

The pyrimidine skeleton has also been found in several marine natural products with interesting biological activities [103]. Among the most notable of these are the crambescidin (9-125) [104] and the batzelladine (9-126) [105] alkaloids which show pronounced bioactivity (Scheme 9.26). Thus, batzelladine A and B are new leads for... 

The validity of the oxauracil strategy for a stereoselective construction of the azabicyclic core has been proven for the syntheses of biologically important polyguanidinium alkaloids, namely, batzelladine A and D [58]. Reaction (7.48) shows that treatment of 41 under the standard free-radical conditions furnished the desired azabicycle in a 77 % yield, in a high diastereoisomeric ratio. Here it can be seen the effect of H donation from the more accessible face of the molecule. 

In an effort to extend the scope of various synthetic studies towards 2-amino derivatives of 1,4-dihydropyridine, Kappe and co-workers performed a microwave-mediated regioselective construction ofnovelpyrimido[l,2-a]pyrimidines (Scheme 3.51)81. This ring system can be found in marine-derived natural products such as Crambescidin and Batzelladine alkaloids. 

Nitrosonium terafluoroborate initiates the cation radical-mediated imino-Diels-Alder reaction of IV-arylimines with IV-vinylpyrrolidinones to give cw-4-(2-oxopyr- (g) rolidin-l-yl)tetrahydroquinolines.175 Also, 2,4,6-triphenylpyrylium tetrafluoroborate catalyses the Diels-Alder addition of IV-arylimines with IV-vinylpyrrolidinone and IV-vinylcarbazole to yield the corresponding 2-oxopyrrolidin-l-yl- and carbazole-9-yl-tetrahydroquinolines.176 The tricyclic core (151) of the batzelladine alkaloids has been prepared by a diastereoselective 4 + 2-annelation of the vinylcarbodiimide (150)... 

The [2+4] diastereoselective annulation of vinyl carbodiimides 48 to cyclic N-alkylimines 49 affords the S,S-diastereomer of the bicyclic dihydropyrimidine 50. This reaction is used in the synthesis of batzelladin alkaloids. 

Butynoate was reacted with TMGA (28) to give p-azido acrylate as a mixture of geometric isomers. The 1,4-conjugate addition product served as the diene component in the [4 + 2] annulation reaction after conversion to vinyl carbodirmides by Staudinger-aza-Wittig condensation with benzylisocyanate [110], These reactions are key steps in the total synthesis of batzelladine alkaloids (Scheme 4.44). 

Patil, A.D., Freyer, A.J., Taylor, P.B. et al. (1997) Batzelladines F-I, novel alkaloids from the sponge Batzella sp. Inducers of p561ck-CD4 dissociation. The Journal of Organic Chemistry, 62, 1814-1819. 

Hua, H., Peng, J., Dunbar, D.C. et al. (2007) Batzelladine alkaloids from the Caribbean sponge Monanchora unguifera and the significant activities against HIV-1 and AIDS opportunistic infectious pathogens. Tetrahedron, 63, 11179-11188. 

Marine alkaloids (-f)-batzelladine A and ( )-batzel-ladine D. Nine novel tricyclic guanidine marine alkaloids were isolated as metabolites of the Crambe genus. Members of the batzelladine alkaloid class exhibit potential antiviral activity in the inhibition of HIV gp 120-Human CD4 binding, as well as potential immunosuppressive... 

Frairklin, A.S., Ly, S.K., Mackin, G.H., Overman, L.E., and Shaka, A.J. (1999) Application of the tethered Biginelli reaction for enantioselective synthesis of batzelladine alkaloids. Absolute coirfigmation of the tricyclic guanidine portion of batzelladine B. J. Org. Chem., 64,1512-1519. 

Yu, M., Podiapsky, S.S., and Snidei B.B. (2008) Synthesis of 7-epiptilocaulin, mirabilin B, and isoptilocaulin. A unified biosynthetic proposal Ibr the ptilocaulm and batzelladine alkaloids. Synthesis and structure revision of netamines E and G. J. Org. Chem., 73,9065-9074. 

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