Natural bioactive alkaloids synthesis

PEROXIDASES AS CATALYSTS IN THE SYNTHESIS OF NATURAL BIOACTIVE ALKALOIDS... 

There are, however, a few examples in which the exclusive participation of peroxidase in the synthesis of natural bioactive alkaloids has been reported. These mainly concern the biosynthesis of some monoterpenoid indole alkaloids, especially the synthesis of a-3 ,4 -anhydrovinblastine (XLVII) [76],... 

The total synthesis of litseaverticillols D, F and G (172 and 173), which are natural products with anti-HIV activity, was achieved recently via a singlet oxygen initiated cascade proposed to be biomimetic (Scheme 64). Finally, allylic alcohols 174a and 174b (Scheme 64) were isolated in a 4/1 ratio via a stereoselective singlet oxygen ene reaction. Stereoisomer 174a is an intermediate in the synthetic route of staurosporine, which is a bioactive alkaloid with hypotensive, antimicrobial and cell cytotoxic properties. 

Total synthesis of complex bioactive natural N-, 0-, and N,0-heterocycles, alkaloids, enzyme inhibitors, and herbicides 99YGK736. 

KitaM, Uemura D (2006) Bioactive Heterocyclic Alkaloids of Marine Origin. 6 157-179 Kiyota H (2006) Synthesis of Marine Natural Products with Bicyclic and/or Spirocyclic Acetals. 5 65-95... 

A complete review on the synthesis of indolizines has appeared <2000HOU(10)745>. This chapter is an extension of the reviews in CHEC(1984) <1984CHEC-I(4)443> and CHEC-II(1996) <1996CHEC-II(8)237>, mainly focusing on the development of synthetic methods aimed at the synthesis of natural alkaloids and important bioactive compounds containing the indolizidine nucleus. 

Some selected alkaloids are readily accessible via the corresponding chromium carbenes. A versatile synthesis of indolocarbazoles 133 and 134, bioactive natural products with interesting protein kinase C inhibiting properties, is based on photobenzannulation. Depending on the nature of the Cj-synthon, dioxy and oxyamino derivatives have been synthesized in good to very good yields (Scheme 46) [96]. 

Bonnet and Ganesan [12] developed a new route toward the solid-phase synthesis of tetrahydro-P-carboline hydantoins, which appear in a diverse array of biologically active alkaloids. Due to the presence of tetrahydro-P-carbolines and diketo-piperazine ring skeletons in several bioactive natural products, these two scaffolds became attractive targets for developing a combinatorial chemistry program. 

The unique structure and extraordinary bioactivity of manzamine alkaloids have attracted great interest from synthetic chemists as one of the most challenging natural product targets for total synthesis. Great efforts have been made to achieve total synthesis of manzamine A and related alkaloids. Methodological studies towards the synthesis of manzamine structural units have also been reported [31-33]. 

The enantioselective total synthesis of the complex bioactive indole alkaloid enf-WIN 64821 was accomplished by L.E. Overman and co-workers." This natural product is a representative member of the family of the C2-symmetric bispyrrolidinoindoline diketopiperazine alkaloids. The stereospecific incorporation of two C-N bonds was achieved using the Mitsunobu reaction to convert two secondary alcohol functionalities to the corresponding alkyl azides with inversion of configuration. The azides subsequently were reduced to the primary amines and cyclized to the desired ib/s-amidine functionality. 

Tyrosine spirolactones are not only promising synthetic intermediates for bioactive natural products such as alkaloids and antibiotics but also synthons useful in peptide chemistry. For example, N-protected tyrosine derivatives 104 and 105, prepared from 2,6-di(ferf-butyl)-4-chloromethylphenol, were electrolyzed at a controlled potential (+1.3-1.4 V Vi. Ag/Ag+) in MeCN to give spirolactones 106 and 107 (64 and 85%, respectively). These spirolactones are used for peptide synthesis, as shown in Scheme 19. 

From the viewpoint of organic synthesis, nature provides us with a number of target molecules, which have novel structures and a variety of biological activities. As already shown in Section II.A, electrochemical oxidation of phenols has been applied successfully to natural products synthesis. Hypervalent (diacyloxyiodo)benzenes have also been proved to be effective for natural products synthesis. Generally, oxidation of o- and p-methoxyphenols in MeOH provides the corresponding o- and p-quinone monoketals, respectively. They are utilized as promising synthons for natural products and related bioactive compounds, as demonstrated by Swenton . Recently, these quinone monoketals have been utilized for syntheses of terpenoids, neolignans, anthraquinones, alkaloids and related compounds. 

---