Petrosin

Scheme 9 Total synthesis of petrosins C (98) and D (99) [40], Experimental conditions i. PhS02CH2Cl, NaOH, DMSO ii. NaOMe, MeOH, rt Hi. (a) -BuLi, THE (b) (Z)-CICH2CH = CHCH2OTBS iv. 5% Na/Hg, MeOH v. (a) -BuLi, THE (b) TBOS replaced by chloride in 104 vi. (a) -BuLi, THE (b) MgBr2-Et20 (c) PhSSPh vii. (NH4)6Mo7024, H2O2 via. IN HCl, THE ix. MsCl, LiCl, 2,6-lutidine, DMF x. NaHMDS, THE xi. p-TSNHNH2, NaOAc, THE, H2O xii. (a) 3 eq. w-BuLi, 2,6-lutidine, THE (b) CH2 = CHCH2I xiii. Na/Hg, THE, MeOH xiv. (a) s-BuLi, TMEDA, ether, (b) CH2 = CHCH2Br...

Scheme 10 Total synthesis of petrosins C (98) and D (99) [41] (contd.). Experimental conditions i. (a) 9-BBN, THE, (b) H2O2 ii. MsCl, EtsN, CH2CI2 in. NaBH4, EtOH iv. aqueous HCl V. EDA, THE, Mel vi. K2CO3, MeOH, H2O...

The bisquinolizidine alkaloid petrosine, C30H50N2O2, was isolated from Pe-trosia seriata 112). IR absorption bands occur at 1712 (—CO—), 2770, and 2810 cm (trans-quinolizidine) protons of a secondary methyl group are at 8 0.94 J = 6.4 Hz) in the H-NMR spectrum. Examination of C-NMR and H-NMR spectra as well as X-ray structural analysis revealed the presence of two quinolizidine fragments in the petrosine molecule (65). They are joined by pen-... 

Macrocyclic quinolizidine or 1-oxaquinolizidine alkaloids, aragu-spongines B-H (236-242) and J (243) (206) and aragupetrosine A (244) (207) were isolated from an Okinawan sponge (Xestospongia sp.) together with the previously known petrosin (245) (208) and petrosin A (246) (209). These alkaloids show vasodilating activity. 

The Mediterranean sponge Reniera sarai is a rich source of new macro-cyclic alkaloids, named sarains, which may be biogenetically related to petrosin (246) or araguspongins (236-243). The structures of sarains 1-3 (247-249) (2/0) and isosarain 1 (250) (211) were clarified on the basis of extensive spectroscopic analyses. The position of the double bond in 249 remains to be determined. The more polar fraction of this sponge contained three UV-absorbing alkaloids, named sarains A-C. The structure of the diacetylated derivative of sarain A (251) was established by X-ray analyis (2/2). 

From a Japanese sponge of the genus Haliclona two cytotoxic alkaloids, haliclamines A and B (252 and 253), were isolated (213). They are proposed to be biogenetic precursors of the petrosins or sarains. 

Two novel alkaloids named manadomanzamines A and B were isolated from the Indonesian sponge Acanthostrongylophom spp. [58]. The compounds exhibited activities against HIV-1 and AIDS-opportunistic fungal infections. Oral and intravenous pharmacokinetic studies indicated that the compounds have low metabolic clearance, a reasonably long pharmacokinetic half-life, which supports the value of these compounds as potential leads for further preclinical assessment and possible development [59]. Another marine sponge, Petrosia similis, afforded two compormds belonging to bis-quinolizidine alkaloids, namely petrosin and petrosin A [60]. Cell assays indicated that these compounds inhibited the early steps of HIV replication. In the extracellular HIV-1 RT inhibition assay, the compounds inhibited HIV-1 RT. 

Aragupetrosine A 795 Araguspongine H Fig. II. Structures of the petrosins and related sponge metabolites,... 

Cimino and Kitagawa s proposals for formation of the petrosin, aragupetrosine and xestospongin/araguspongine skeletons [37, 38, 46,49],... 

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