Alkaloids oxomaritidine

Ley, S.V., Schucht, O., Thomas, A.W., Murray, P.J. (1999) Synthesis of the Alkaloids ( )-Oxomaritidine and ( )-Epimaritidine Using an Orchestrated Multi-Step Sequence of Polymer Supported Reagents. Journal of the Chemical Society Perkin Transactions I, 1251-1252. 

Ley SV, Baxendale IR (2002b) New tools and concepts for modern organic synthesis. Nat Rev Drug Disc 1 573-586 Ley S V, Massi A (2000) J Comb Chem Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem michael addition reactions and subsequent combinatorial decoration. 2 104—107 Ley SV, Schucht O, Thomas AW, Murray PJ (1999) Synthesis of the alkaloids ( )-oxomaritidine and ( )-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1 1251— 1252... 

Supported reagents have been used in synthesis since 1946, but their application in natural product synthesis has been very limited. Indeed, where they had been used, it was only to effect a spedlic transformation where conventional systems had previously failed. Our group, however, has sought to develop the application of immobilized systems to complex synthetic challenges in a multistep mode. The first serious application of supported reagents for natural product synthesis was published in 1999. ° Here, concise routes to two amarylUdaceae alkaloids, oxomaritidine (1) and epimaritidine (2), in just five and six steps, respectively, were reported (Scheme 6.1). 

SCHEME 6.1 The first orchestrated and successive application of supported reagents in the synthesis of the amaryllidaceae alkaloids oxomaritidine and epimaritidine. Copyright 2006 Taylor Francis Group, LLC... 

Baxendale, I.R., Deeley, J., Griffiths-Jones, C.M., Ley, S.V., Saaby, S., Tranmer, G.K. (2006) A Flow Process for the Multi-Step Synthesis of the Alkaloid Natural Product Oxomaritidine A New Paradigm for Molecular Assembly. Chemical Communications, 2566-2568. 

Baxendale IR, Deeley J, Griffiths-Jones CM, Ley SV, Saaby S, Tranmer GK (2006) A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine a new paradigm for molecular assembly. Chem Commun, p 2566-2568... 

Oxidative phenolic coupling. Biosynthesis of the alkaloid narwedine (3) is known to involve oxidative phenolic coupling of norbelladine derivatives (1), but the usual oxidants for such coupling in vitro convert 1(R = H) into the oxomaritidine skeleton (4) rather than 3. A new biomimetic synthesis of 3 involves the palladacycle 2, formed by reaction of 1(R = CH3) with Li2PdCl4, which is known to form complexes with allylic amines or sulfides (8,176-177). Oxidation of 2 with thallium(III) trifluoroacetate effects the desired coupling to give 3. 

The Ley research group [76] developed a flow process for the multistep synthesis of ( )-oxomaritidine, an alkaloid found in the Amaryllidaceae family, known to have antineoplastic activity (Scheme 34) [77, 78]. The route does not involve intermediate purification of the products, which is necessary in the previously reported... 

Ley SV, Schucht O, Thomas AW et al (1999) Synthesis of the alkaloids (t-/-)-oxomaritidine and (-l-/-)-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1(10) 1251-1252... 

L-phenylanine alkaloids alkaloids Crinine Eloramultine Galanthamine Galanthine Haemanthamine Lycorine Lycorenine Maritidine Oxomaritidine Vittatine... 

Studies directed toward the synthesis of amaryllidaceae alkaloids provide instructive examples of the combined use of spirocylization and Michael addition pathways in phenolic oxidations (03MI1). For example, treatment of the norbelladine derivative 164 with BTIB leads, by way of C,C-bond formation, to the spiroannulated azepine 165 (Scheme 47) (96JOC5857, 98JOC6625). Hydrolysis of the amide moiety in 165 results in Michael addition of the nitrogen center to the dienone ring and affords ( )-oxomaritidine (166). BTIB-oxidation of the appropriate... 

The multi-step synthesis of the alkaloid natural product ( )-oxomaritidine was performed with microfluidic pumping systems feeding various packed columns containing immobilized reagents, catalysts, scavengers or catch-and-release... 

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