Marine alkaloids synthesis

Lindsay, B. S., Christiansen, H. C. and Copp, B. R. 2000. Structural studies of cytotoxic marine alkaloids Synthesis of novel ring-E analogues of ascididemin and their in vitro and in vivo biological evaluation. Tetrahedron, 56 497-505. 

Progress in total synthesis of marine alkaloids, aaptamines 99H(50)549. 

Reports on total synthesis of naniral products using nitrones papers are as follows marine alkaloid lepadiformine fRef 92 and fi-lactam antibiotics fRef 93, ... 

The group of Molina and Fresneda employed even two different types of anionic domino processes in their total synthesis of the novel marine alkaloid variolin B (2-295) (Scheme 2.67) [150]. It is generally accepted that marine organisms are among... 

To date, there are only few examples of applying the VNS reaction in the synthesis of natural products. Several natural products such as O-methylnordehydrobuffotenine (Scheme 9.10),91 an alkaloid of animal origin, l,3,4,5-tetrahydro[cd]indole (Scheme 9.11),92 and 7,8-dimethoxy-2-oxo-l,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline as key intermediates for marine alkaloids (Scheme 9.12)93 have been prepared via VNS reactions. 

Perhydropyrido[l,2-A][l,2]oxazines have been utilized as key intermediates in a stereospecific total syntheses of (—)-pumiliotoxin C and 5-< />z-pumiliotoxin C <1996J(P1)1113>, and the marine alkaloids (—)-lepadins A, B, and C and macrocyclic dilactones, (+)-azimine and (+)carpaine <20000L2955, 2001JOC3338, 2003OL3839>. In the total synthesis of the marine alkaloids ( )-fasicularin and ( )-lepadiformine, perhydro[l,2]oxazino[3,2 /]quinolines were used to control the stereochemistry <2000JA4583, 2000TL1205>. 

The ring system 413 is an intermediate in the synthesis of the tricyclic core of the marine alkaloids sarains A-C (Scheme 32) <1998JOC8096>. 

The pyrrolopyridooxazine 485 is an intermediate in the 12-stage synthesis (overall yield 6%) of the antitumor marine alkaloid, veiutamine (Equation 213) <1999TL1713>. 

Synthesis of a tricyclic core of marine alkaloid variolin B has been achieved in three steps. The key reaction involves tandem deoxygenation and cylization of a triarylmethanol 187 using a combination of trifluoroacetic acid (TFA) and triethylsilane (TES). The use of 4.3equiv of TFA and 8.1 equiv of TES minimizes the formation of side products 188, 189 and allows the formation of the desired product 190 in 34% yield (Scheme 5) <2005JOC6204>. 

Some analogues of the marine alkaloid variolin B2 were prepared as potential cytotoxic agents. The compound 56 is particularly interesting as its synthesis included the simultaneous formation of two pyrimidine rings <06JMC1217>.-... 

Buchwald parlayed the powerful Buchwald-Hartwig aryl amination technology [439-447] into a simple and versatile indoline synthesis [448-452], For example, indole 368, which has been employed in total syntheses of the marine alkaloids makaluvamine C and damirones A and B, was readily forged via the Pd-mediated cyclization shown below [448], This intramolecular amination is applicable to the synthesis of -substituted optically active indolines [450], and o-bromobenzylic bromides can be utilized in this methodology, as illustrated for the preparation of 369 [451]. Furthermore, this Pd-catalyzed amination reaction has been applied to the synthesis of arylhydrazones, which are substrates for the Fischer indole synthesis [453,454],... 

The basic alkaloid in Pilocarpus jaborandi (Rutaceae) is pilocarpine, a molecule of which contains an imidazole nucleus and is also used as a clinical drug. During alkaloid synthesis, L-histidine can produce the manzamine nucleus (Figure 27). These alkaloids are quite widespread, though they were first isolated in the late 1980s in marine sponges. They have an unusual polycyclic system and a very broad range of bioactivities. Common alkaloids with this nucleus include manzamine A, manzamine B, manzamine X, manzamine Y, sextomanzamine A and so on. 

A, A -Bis(phenacyl)-/i-toluenesulfonamides 173 are readily synthesized by reactions of /(-toluenesulfonamide with phenacyl bromides or/i-toluenesulfonyl chloride with phenacyl amines, and converted into 2,6-diarylpyrazines 174 in high yields by treatment with methyl hydrazinocarboxylate (Equation 27) <1998HAC341>. Another constmction involving cyclization at the final stage by treatment with ammonia was conducted for the synthesis of the framework of a marine alkaloid <2000H(53)15S9>. 

As Moody and co-workers (173) discovered, isomtinchnones can occasionally form even when they are not the desired product Thus, these workers inadvertently obtained an oxazolidinedione via an isomtinchnone rather than the desired oxoindo-line when a diazo compound was treated with rhodium(II) perfluorobutyramide in their studies leading ultimately to a synthesis of the marine alkaloid convolutamy-dine C. 

The marine alkaloid sarain A 383 features an exceptionally challenging pentacyclic architecture (Figure 6). To date, 383 has not succumbed to a total synthesis. Two groups however have completed the tricyclic core of 383 and have annulated the western 13-membered ring using quite similar RCM approaches. " The results obtained with... 

The photochemical electrocyclization of conjugated iminium salts 160, formed by protonation of 2-azadienes 159, led to isoquinolin-4-ones 162, presumably through hydrolysis and oxidation of the dihydroisoquinoline intermediates 161 (85TL5213) (Scheme 39). A closely related reaction served as the key step for a short synthesis of the pentacyclic marine alkaloid ascididemin as reported by Moody, Rees, and Thomas [90TL(31)4375 92T3589] the central reaction involves a 67r-electron pho-tocyclization of a syn- aza stilbene in sulfuric acid. 

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