Amathaspiramides

The tetrahydro derivative 47 was obtained from an unexpected cyclization of the nitro compound 46 by deprotonation with NaOMe in methanol followed by a treatment with TiCh, then with H20. This side product was observed in the approach of amathaspiramide F 48 (Equation 4) <2002AGE4556>. 

Amathaspiramide E (128) from the New Zealand bryozoan Amathia wilsoni exhibits strong activity in the antiviral assay against Polio virus [102],... 

Tyrosine-derived metabolites in this section do not include spiro-cyclohexadienyl-isoxazolines and related compounds (Sect. 3.22.3.3) or bastadins (Sect. 3.22.3.4), but they do include tyrosine-derived alkaloids that were covered in the Alkaloids section in the first survey (1). The prolific bryozoan Amathia convoluta, collected in Tasmania, has yielded amathamide G (1953) (1814), the latest of several amath-amide alkaloids from the genus Amathia (1). A Florida collection of this animal furnished the new convolutamines A-E (1954—1958) (1815), F (1959), and G (1960) (1425), and a Tasmanian sample of this bryozoan afforded convolutamine H (1961) (1319). A study of Amathia convoluta from the North Carolina coast has yielded volutamides A-E (1962-1966) (1816). Volutamides B and C reduce feeding by the pinfish (Lagodon rhomboids) and the urchin (Arbacia punctulata), respectively, and volutamides B and D are toxic toward larvae of the hydroid Eudendrium carneum. The New Zealand Amathia wilsoni contains the six novel amathaspiramides A-F (1967-1972) (1817). 

Morris BD, Prinsep MR (1999) Amathaspiramides A-F, Novel Brominated Alkaloids from the Marine Bryozoan Amathia wilsoni. J Nat Prod 62 688... 

Nitroalkanes have also been reduced to oximes with mixtures of SnCh O, PhSH, and Et3N. 11 As shown below, these conditions were used to achieve the transformation of 25 to 26 in 85% yield. The oxime products of these reactions can be converted to ketones under mild conditions via hydrolysis or oxidation. This method was employed in a key step of Trauner s recent synthesis of (-)-amathaspiramide F (see Section 7.7.6).12... 

Out of six amathaspiramides, only four amathaspiramides A-C (129-131) and E (133) were evaluated for their biological activity as a cytotoxic, antiviral, antimicrobial and for P388 murine leukemic. Amathaspiramides A (129) and E (133) exhibited moderate cytotoxic activity against the BSC-1 cells (1+, 40 pg/well), while amathaspiramides B (130) and C (131) were foimd inactive at the tested concentrations. Amathaspiramide E (133) was found highly active (4+, 40 pg/well) against the Polio virus Type 1 (Pfizer vaccine strain). 

Because of their unique structures and skeleton, various groups have targeted to synthesize amathaspiramides. First total synthesis of (-)-amathaspiramide F (134) was reported by Hughes and Trauner, and it is depicted in Scheme 12 [63]. The synthesis was started by taking AA -acetal 136, which was synthesized from L-proline 135. 

Acetal 136 on enolization followed by conjugate addition with nitro olefin 122 gave alkylated products 137 and 138 in a diastereomeric mixture of 10 1. Compound 137 was proceeded for amathaspiramide F synthesis, which on hydrolysis followed by N-trifluoroacetyl protection gave amide 139. Nitro group of compound 139 was converted into oxime 140. Hydrolysis of oxime followed by cyclization and then deprotection of N-trifluoroacetyl group gave amathaspiramide F (134) Scheme 12 [63],... 

Amathaspiramide F has also been synthesized by Sakaguchi and coworkers [64, 65], and they started the synthesis by taking a-hydroxy-a-ethynylsilane as a starting material. The key step of the synthesis was enolate Claisen rearrangement. While ( )-amathaspiramide F has been synthesized by Soheili and Tambar [66]. They started the synthesis by taking substituted phenyl allyl carbonate and A-substituted proline ester. 

The key step of the synthesis was palladium -catalyzed allylic amination/[2,3]-Stevens rearrangement. Amathaspiramides A-F (129-134) were synthesized by Chiyoda et al. [67]. They started the synthesis by taking 3-methoxyphenacyl bromide and the key step was the reduction of lactam moiety to the cyclic imine by Schwartz s reagent, [Cp2Zr(H)Cl]. 

Morris, B. D., Prinsep, M. R. Amathaspiramides A-F, novel brominated alkaloids from the marine bryozoan Amathia wilsoni. J. Nat. Prod. 1999, 62, 688-693. 

Scheme 15.42 Diastereoselective r2.31-Stevens rearrangement for the synthesis of amathaspiramide F.

In a total synthesis of ( )-amathaspiramide F, via a tandem palladium-catalysed allylic amination/[2,3]-Stevens rearrangement, the unexpected diastereoselectivity of the [2,31-rearrangement has been reported to be controlled by substitution patterns of the aromatic ring (Scheme 55)7 ... 

Synthesis of (i)-Amathaspiramide F Stereochemical Switch of a [2,3]-Stevens Rearrangement... 

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