Structural and stereochemical revision of isocyanide and isothiocyanate amphilectenes from the Caribbean marine sponge Cribochalina sp.

Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes

“…8,9 Several structurally related natural products as well as a small number of synthetic analogs prepared from diisocyanide 1 also exhibit antimalarial and antimycobacterial potential. 10 Whilst comparison among their activities reveals that the biological activity is generally dependent on the presence of the isocyanide functionality, the structural features of the carbon backbone and the location of the isocyanide groups also seem to play a pivotal role.…”

“…13 We targeted diisocyanide 1 as a suitable starting material, a well-known antimalarial and antimycobacterial pharmacophore accessible to us which contains both a rigid amphilectane skeleton and two isocyanide “handles” with potential for further synthetic elaboration. 8 We anticipated that comparison among the biological activities exhibited by the strickly related amphilectane analogs with those of 1 would reveal definite structure-activity relationships. While the isothiocyanate moiety is found in many natural products only two isothiocyanate-containing amphilectane diterpenoids with antiplasmodial activity have been documented.…”

Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold

“…6 This is not only due to the lack of compound supply, but equally important, the limited availability of general methods based on mild reaction conditions required for further functional group manipulations. For instance, the synthesis of complex natural products like 8,15-diisocyano-11(20)-amphilectene [(–)-DINCA] ( 3 ) 7 and analogues required for structure-activity relationship (SAR) studies, poses a difficult challenge, often involving rather lengthy syntheses with introduction of the isocyanide functionality late in the synthesis. 8 An alternative approach to drug discovery, which we have explored previously, is to use an abundant natural product as a scaffold or building block and to convert it into a small focused library of analogues.…”

Chemical Examination of the Sponge Phycopsis sp.

“…[1][2][3][4][5][6][7] Interestingly, many of these nitrogenous functional group containing terpenes and 5a,8a-epidioxy sterols have been found to possess different biological activities. [8][9][10][11] Previously, phenolic derivatives 12) and 4-thiocyanatoneopupukeanane 13) were reported from the sponge species of Phycopsis.…”

“…collected from Mandapam coast, India. Herein we report the isolation, and structure determination of the two new compounds; i) bisabolene type sesquiterpenoid, 7a,8a-epoxy theonellin isothiocyanate (1) and ii) 5a,8a-epidioxyergosta-6Z,22Z,25-trien-3b-ol (2), together with two known related sesquiterpenes, theonellin isothiocyanate (3) 15) and theonellin formamide (4) 15) from the sponge Phycopsis sp. Effect of 2 on cell proliferation of HL-60 (myeloid leukemia) and U937 (leukemic monocyte lymphoma) was investigated.…”