Narciclasine type alkaloids

Recently, oxidation of a halobenzene using a microbiological procedure was found to give optically active 3-halo-l,2-ciy-dihydroxycyclohexa-3,5-diene in good yield. This compound has received the attention of chemists for constructing ring C in the narciclasine-type alkaloids (153). 

Solvent a DMSO-4, b CDCI3-CD3OD, c CD3OD, d CDCI3. TABLE XV. H NMR Data of Narciclasine-Type Alkaloids. ... 

Cherylline-type alkaloids derived from tetrahydroisoquinoline Narciclasine-type alklaloids and... 

Among these alkaloids, narciclasine (lycoricidine)-type alkaloids are highly oxygenated compounds, the significant antitumor activity of which attracts the attention of biologists and pharmacologists. Recent developments in analytical techniques, as well as isolation procedures, have resulted in the rapid characterization of many structures. In the sections on the alkaloids that have been isolated for the first time from the Amaryllidaceae plants, not only the novel, but also the known, structures have been included. This chapter is a review of the Amaryllidaceae alkaloids that have appeared in the literature (1-7) since a previously published review in this series (S). 

Regarding the synthesis of the narciclasine (lycoricidine)-type alkaloids, an important strategic element is how to construct the functionalized ring C in these alkaloids. Therefore, extensive efforts to explore a new method for preparing a key intermediate have been made. 

The alkaloids derived from 5,10b-ethanophenanthridine (crinine and haemanthamine types), 2-benzopyrano[3,4c]indole (tazettine type), phenanthridine (narciclasine type) and 5,11b-methanomorphanthridine (montanine type) originate from a para-para oxidative phenolic coupling (Fig. 9). 

Chemical routes to narciclasine and 7-deoxypancra-tistatin (narciclasine type) as well as galantamine are described in the synthetic section of this chapter. The biosyntheses of these two types of Amaryllidaceae alkaloids are described in the following, while the discussion of other interesting classes of Amaryllidaceae constituents is omitted. 

A truly biomimetic route to alkaloids of the narciclasine type has not been published yet. Nevertheless, very interesting protocols for the coupling of the six-membered ring motifs have been employed in the preparation of these compounds. Transition metal-catalyzed couphng reactions play an important role in the preparation of Amaryllidaceae alkaloids, and Hudlicky s synthesis of narciclasine highlights this approach [171,172]. Keck utihzed radical reactions and... 

The majority of the approaches that have been adopted for the synthesis of narciclasine (215), lycoricidine (214), and related alkaloids have involved the strategy of constructing the ring system in the order A — C —> B. There have also been examples of the A — BC and C —> A —> B type. 

Despite a considerable amount of recent work on reactions of vinyl silanes with various kinds of imines [48,49], scant attention has been paid to N-sulfonyl imi-nes in this area. A single study of a vinyl silane/N-sulfonyl imine reaction has been published by McIntosh and Weinreb in the context of an approach to the total synthesis of [1, 3]-dioxolophenanthrene structural types of Amaryllida-ceae alkaloids such as narciclasine (137), lycoricidine (138) and pancratistatin (139) [50]. The substrate used in this approach was vinyl silane aldehyde 140, prepared enantiomerically pure in a straightforward manner from L-arabinose (Scheme 26). The N-tosyl imine derived from this aldehyde could be generated in two different ways. The first involved combination of 140 with N-sulfinyl-p-toluenesulfonamide at 80 °C, followed by exposure of the imine to BF3 etherate at 0°C, leading to a single cyclization product 142 in 36% yield. The second procedure was to simply react aldehyde 140 with p-toluenesulfonamide and BF3 etherate (-78°C -rt) to afford a 9.5 1 mixture of 142 144 in -80% yield. It was pro-... 

The structural revision of narciprimine led to a more detailed investigation17 into the identity of the related alkaloid narciclasine, which had been assigned structure (20) by other workers. On the basis of interpretation of u.v. and n.m.r. spectra in comparison with those of other alkaloids of this structural type and of chemical degradation, the revised structure (21) for narciclasine has been advanced. Synthetic work towards the final solution of this structural problem is under way.17... 

Narcissus alkaloid structures. Narciclasine and Montanine types. 

The large number of structurally diverse Amaryllidaceae alkaloids are classified mainly into nine skeleton types, for which the representative alkaloids are norbelladine, lycorine, homolycorine, crinine, hemanthamine, narciclasine, tazettine, montanine, and galanthamine (Fig. 1). With the aim of unifying the numbering system of the different skeleton types, Ghosal s model will be used in this review (20). 

Narcissus Alkaloid Structures. Narciclasine and Montanine Types. 

Skeleton types LY, lycorine HL, homolycorine HT, hemanthamine TZ, tazettine NC, narciclasine MN, montanine GA, galanthatnine. Alkaloid names see Tables I-Vn. 

---