Calyculines

This methodology has been further applied in the total synthesis of the natural products FK 50696, calyculin A97b, ionomycin97, lepidicin A97c, macbecin I97a and others97d. 

This effect is particularly well documented for y - and -amino acid residues [217, 218] which in several natural products (bleomycin A2 [219], calyculins [220]) have been shown to play a substantial role in the pre-organization of the whole molecule into its bioactive conformation. For example, changes in the substitution pattern of the y-amino acid linker in bleomycin A2 result in reduced DNA cleavage efficiency [219]. In the case of y-peptides, changing the relative configuration like or unlike of y " -amino acids has been used as a strategy to generate different local conformations (Fig. 2.34) suitable either for the construction of helices [201] or turns ]202-204]. 

A portion of the side chain of calyculin was prepared by a tandem reaction sequence that combined an alkenylzinc reagent with 2-bromoethenylboronate, followed by Suzuki coupling with a vinyl iodide in the same pot.230... 

FIG. 4. Ultrastructure of vascular smooth muscle of the rabbit inferior vena cava revealed with electron microscopy. Serial cross-sections of VSMCs are shown in series 1 (panel A—D) and series 2 (panel E—G). Series 1 illustrates the close spatial apposition between the superficial SR sheet and the PM with the apices of the caveolae perforating through the superficial SR sheets to come into contact with the bulk cytoplasm. The membranes of the PM (dotted line) and the SR (solid line) in panel A-D are outlined to the right of the respective panels. The close apposition between the superficial SR sheet, the PM and the neck region of the caveolae creates a narrow and expansive restricted space. Series 2 illustrates the perpendicular sheets of SR, which appear to arise from the superficial SR sheets. Mitochondria also come into close contact with the perpendicular SR sheets. Panel H contains a stylized illustration of the close association between the superficial SR sheet, which is continuous with the perpendicular sheet, the perforating caveolae (C), the PM and a mitochondrion (M). Panel I shows calyculin-A mediated dissociation of the superficial SR sheets from the PM (see arrows). The black scale bar indicated represents 200 nm of distance. 

Sakurada K, Zheng B, Kuo JF (1992) Comparative effects of protein phosphatase inhibitors (okadaic acid and calyculin A) on human leukemia HL60, HL60/ADR and K562 cells. Biochem Biophys Res Commun 187 488-492... 

In their synthesis of (+)-calyculin A and (—)-calyculin B, Smith and co-workers observed partial epimerization when the (3-hydroxy amide 4 was reacted with SOCI2 despite the mild reaction conditions, 4 °C in tetrahydrofuran (THF)." The mechanism of this epimerization was not discussed (Scheme 8.5). 

During studies toward the synthesis of calyculin C, Karisalmi and Koskinen noted the particular stability of boronate ester 65, although details were not given <200481331 >. 

Following the first report of tumor promotion by okadaic acid, additional tumor promoters of the okadaic acid activity class have been identified, e.g., microcystin [513,514], and calyculin derivatives, Fig. (63) reported in marine sponges such as Discodermia calyx [515] and Theonella swinhoei [516] as potent inhibitors of tumor cell proliferation. A two-sponge association, Poecillastra sp. and Jaspis sp., yielded cytotoxic toxins which exhibited selective activity against several tumoral cell lines [517],... 

Tautomycin. a secondary metabolite from Streptontyces spiroi erti-citlatiis was first isolated by l.sono, who also established its structure.1 The unusual structural feature of this compound is an unsaturated anhydride group, which in aqueous medium is in equilibrium with the free acid. This probably is essential to the compound s biological activity, as is suggested by its structural relationship to such substances as the calyculins or okadaic acid.1... 

The Japanese sponge Discodermia calyx has yielded the new calyculin, calyculin J (1669) (1631). The highly toxic (ichthyotoxicity, hemolytic activity) prymnesin-1 (1670) and -2 (1671), possessing unprecedented structural complexity, were characterized from the red tide alga Prymnesium parvum (1632-1634). 

Matsunaga S, Wakimoto T, Fusetani N (1997) Isolation of Four New Calyculins from the Marine Sponge Discodermia calyx. J Org Chem 62 2640... 

Tzivion, G., Luo, Z.J., and Avruch, J. (2000). Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J. Biol. Chem. 275, 29772-29778. 

Scheme 12.15. Synthesis of a calyculin fragment using a three-component Negishi/Suzuki cross-coupling, by Smith and co-workers [46]. THF = tetrahydrofuran.

Fig. 25 BVMO-catalyzed synthesis of a precursor to calyculin A and tirandamycin...

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