Alkaloids, marine

It is interesting that applications of inverse-detected 2D NMR experiments in the elucidation of marine alkaloid structures presently outnumber terrestrial applications. Most probably, this situation has arisen because there 

Although probably not significant, it is interesting that the first applications of inverse-detected 2D NMR techniques in the study of marine alkaloids were applied to quinoline-based alkaloids. There have also been a sizeable number of isoquinoline and acridine-derived marine alkaloids reported. Thus, we will begin our survey of marine alkaloids with these groups. 

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

Biogenesis of manzamine alkaloids ((3-carboline marine alkaloids) 97H(46)765, 97YGK1114. 

Perhydropyrido[l,2-A][l,2]oxazines are applied as key intermediates in a stereospecific total syntheses of (-)-pumiliotoxin C and 5-e/ /-pumiliotoxin C(96JCS(P1)1113), and the marine alkaloid)—)-lepadins A, B, C (OOOL2955). (2-Pyridyl)propionic acids 13 can be regioselectively prepared via 2,3,4, 4fl,7,8-hexahydropyrido[l,2-A][l,2]oxazin-2-ones 12 (00OL4007). 

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

Fig. 10 Various RCM substrates used in synthetic work directed to the marine alkaloid sarain (285)...

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... 

A potentially useful approach to the marine alkaloid papuamine based on INOC strategy is proposed as shown in Scheme 8.21. In fact, a tnms-hydrindane intermediate has been synthesized in racemic form using a model sequence of reactions involving a nitrile oxide cycloaddition as a key step (Eq. 8.69).106... 

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. 

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>.-... 

The Paal-Knorr reaction was also employed by Steglich in likely biomimetic approaches to the marine alkaloids lamellarin L <00CEJ1147> as well as purpurone and ningalin C <00TL9477>. The overall approach employed herein involved initial oxidative coupling of two arylpyruvic acids followed by condensation of the resulting 1,4-diketones with suitable... 

In the course of their successful syntheses of the marine alkaloids nortopsentins A-D, Kawasaki and co-workers were able to prepare selectively boronic acid 103 from 1 -(tert-butyldimethylsilyl)-3,6-dibromoindole (102) and effect Suzuki couplings to give 3-arylindoles 104 in good yields [117]. Complementary to this chemistry is the direct Pd-catalyzed reaction of 102 with arylboronic acids to give 6-aryl-3-bromoindoles 105 [117]. 

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],... 

Lindsay, B. S., Barrows, L. R. and Copp, B. R. 1995. Structural requirements for biological activity of the marine alkaloid ascididemin. Bioorganic and Medicinal Chemistry Letters, 5 739-742. 

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>. 

During the synthetic efforts of Heathcock and co-workers toward the complex marine alkaloid sarain-A (Scheme 3.80), he outlined an elegant intramolecular, azomethine ylide cycloaddition, as one of the key stages in the construction of the central core (76). Of the generation methods known for azomethine ylides, thermolysis of aziridines was selected in this instance. The azomethine ylide... 

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. 

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