Alkaloid Synthetic Studies

Evodiamine, the alkaloid from the Chinese drug plant Evodia rutaecarpa Benth. and Hook., has also been called rhetsine and its oxidation product rhetsinine, which is also found in nature, was shown to be the diamide (53). Recently a hypotensive red alkaloid isolated from the Brazilian plant Hortia arborea Engl, was given the name hortiamine. Degradation and synthetic studies have shown it to possess the structure (55). It was found together with another... 

Synthetic studies on alkaloid pumilliotoxin C using Pd-promoted cyclization 98YGK818. 

Daikon and wasabi phytoalexins are weak fungicidal alkaloids having a stabilized 1-methoxyindole structure. Relying on the expectation that more potent substances can be found among their derivatives, synthetic studies are in progress according to the method developed in Scheme 22 in Section IV.G. 

The C2o-diterpene alkaloids have long served as classic targets within the field of natural product synthesis [14], Total syntheses of four C2o-diterpene alkaloids have thus far been reported atisine [15], veatchine [16], garryine [17], and napelline [18]. In spite of this progress, synthetic efforts toward the hetisine alkaloids have been relatively sparse. Prior to our work in the area, these efforts include one total synthesis and five synthetic studies. 

Alkaloid chemistry marine cyanobacteria, 57, 86 (2001) synthetic studies, 50, 377 (1998)... 

Halichlorine (1) (Fig. 11.1) is an alkaloid which was isolated from the marine sponge H. okadai Kadota (Kuramoto et ah, 1996). This compound was revealed to be a novel alkaloid containing an azaspiro[4.5]decane skeleton clarified by detailed spectroscopic analyses. The absolute stereostructure was confirmed by many synthetic studies (Arimoto et ah, 1998 Clive et ah, 2005 Liu et ah, 2009 Trauner et ah, 1999). Halichlorine was shown to inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells. Drugs that block the inflammatory stimuli-induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina, and noncardiovascular inflammatory diseases (Kock et ah, 1995). We introduce here the recent aspects of the biological and physiological activities of halichlorine. 

The third and in many ways most creative phase of George Buchi s career had its roots in his doctoral work at ETH, where he had undertaken the synthesis of degradation products of certain triterpenes. Synthetic studies on natural products has always flourished in George s laboratory at MIT, but with his growing interest in complex alkaloid came the opportunity to ex-... 

Lycorine is an alkaloid that has attracted attention from both the synthetic community and pharmacologists. Prior synthetic approaches have included inter-and intramolecular Diels-Alder cycloaddition. Based on a similar retrosynthetic disconnection, Padwa and co-workers (106,109) chose to use a push-pull carbonyl ylide cycloaddition with a disubstituted pyrrolidinone core to generate a tricyclic substrate. The major difference for this synthetic study was the availability of a labile proton a to the carbonyl moiety (Scheme 4.53). 

In an effort to extend the scope of various synthetic studies towards 2-amino derivatives of 1,4-dihydropyridine, Kappe and co-workers performed a microwave-mediated regioselective construction ofnovelpyrimido[l,2-a]pyrimidines (Scheme 3.51)81. This ring system can be found in marine-derived natural products such as Crambescidin and Batzelladine alkaloids. 

In addition, there are many important nonantibiotic uses of 2-azetidinones in fields ranging from enzyme inhibition [15-21] to gene activation [22], Systems containing one carbon atom common to two rings, spirocyclic compounds, represent an important structural organization. Spirocyclic p-lactams (Fig. 3) behave as p-tum mimetics [23-26] as well as enzyme inhibitors [27, 28], they are precursors of a,a-disubstituted p-amino acids [29-32], and the spiranic p-lactam moiety is present in chartellines and chartelamides [33-38], a family of marine natural products. Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described [38],... 

Kajii S, Nishikawa T, Isobe M (2008) Chem Commun 3121, Synthetic studies and biosynthetic speculation inspired by an unexpected reaction on the marine alkaloid chartelline C have been described... 

During synthetic studies on the benzophenanthridine alkaloids, the nitrile ester 1 was treated with sodium hydride in THF in the expectation that a Thorpe-Dieckmann type of reaction would... 

Tohma H, Harayama Y, Hashizume M, Iwata M, Egi M, Kita Y (2002) Synthetic Studies on the Sulfur-Cross-Linked Core of Antitumor Marine Alkaloid, Discorhabdins Total Synthesis of Discorhabdin A. Angew Chem hit Ed 41 348... 

These reactions have been applied to synthetic studies on biologically active compounds such as l/ -methylcarbapenem (87), the antileukemic principle, pareitropone (88), and the potentially antiinflammatory marine alkaloid, halichlorine (89). 

An interesting account of the early synthetic studies on the Lycopodium alkaloids has appeared.10... 

Synthetic Studies directed toward the Diterpenoid Alkaloids.—In studies directed toward the synthesis of the C19 diterpenoid alkaloids, Chatterjee has reported45 the preparation of intermediate (150) by a very unusual synthetic sequence. 

The antitumor activity displayed by camptothecin (28) and its analogues has led to a great deal of interest in such compounds.36 Camptothecin is a complicated alkaloid to isolate, and analogues, which are of biological interest, are synthesized from the natural product itself.37 This need to access a wide range of analogues has led to a need for synthetic studies directed toward the development of a concise, yet inexpensive, total synthesis of camptothecin. 

SYNTHETIC STUDIES ON BIOLOGICALLY ACTIVE ALKALOIDS STARTING FROM LACTAM-TYPE CHIRAL BUILDING BLOCKS... 

SYNTHETIC STUDIES ON BIOLOGICALLY ACTIVE ALKALOID STARTING FROM LACTAM 68... 

Considerable effort continues to be expended on the synthesis of alkaloids of this group and on studying further their interconversion. However, an efficient synthesis of dihydroantirhine, uncontaminated by epimers, still eludes investigators. In the most recent synthetic study it was shown that hydrogenation of the acetate of the tetracyclic base (91a), prepared earlier,700 followed by deacetylation, affords a mixture of the C-20 epimeric 3-epidihydroantirhines (91b).706... 

Synthetic studies on the Salamander alkaloids have been reviewed.67 The synthesis of 18-amino-steroids that are related to the alkaloid batrachotoxin has been discussed.68... 

The structure of the (+)-rubremetinium cation (129) 119-123), the mild oxidation product from emetine (1) 1,121) or O-methylpsychotrine (7) 1,86), and those of its hydrogenation products, (—)-A(or a)-dihydroru-bremetine (131) 120,121,124-126), (+)-B(or / )-dihydrorubremetine (132) 120,121,124-126), and (+)-tetrahydrodehydroemetine (133) 121,124, 126), have been inferred from the early studies summarized in Chapter 3 of Volume XIII and elsewhere 4,5). In early synthetic studies of ( )-emetine (1) and ( )-0-methylpsychotrine (7), ( )-rubremetinium bromide (129 -Br) 41,54,55,57) and iodide (129-1-) 51,52) were prepared by dehydrogenation of synthetic alkaloids of mixed or unknown stereochemistry in order to compare with the natural materials. On the basis of structure... 

Manzamine alkaloids have been the subject of numerous synthetic studies owing to their novel molecular structure coupled with promising biological properties. Most of the synthetic studies on manzamine alkaloids focused on the construction of the ABCDE pentacyclic lower half of the manzamine structure. 

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