___________________
____________________
The massadines, axinellamines, and palau'amines are all dimeric pyrrole imidazole alkaloids, marine-derived products. These alkaloids are stereohemically challenging puzzles, but hold great potential for advancing chemical synthesis. The high nitrogen content of these compounds tests chemoselectiity control in experiments and the diverse confromations of these molecules may be related to the biochemical pathways to their formations. The discovery of a relationship between these could lead to greater understanding and simplification of chemical syntheses.
_ _______________________________________
massadine (R = OH or Cl)__________________axinellamine (R=H or CH3)_________________________palau'amine
Through a series of steps, 1,9-dideoxy-pre-axinellamine was synthesized. The reaction step we are focused on is the last step: The conversion of product 19 to final product 5 (Figure 1). Product 19 is an intermediate product in a reaction scheme to produce 1,9-dideoxy-pre-axinellamine. In a solution of TFA, Product 19 undergoes a Staudinger Reaction to form an intermediate compound. This compound's Boc groups then react to for Product 5.
___Figure 1______________
____
Product 19 to Product 5 (2 steps)
1.0 equivalents of compound 19 was added to 4.1 equivalents of PPh3 in a solution of CH3CN. The reaction was allowed to run for 40 minutes at 60 C. Water was then added and the reaction ran for 1.5 hours. Then, 6.1 equivalents of compound 20 was added to 10.2 equivalends of EDCL with NEt3 into the existing solution. The reaction was run for 1.5 hours at 23 C (yield 45%). The mixture was then added to a 2:1 solution of TFA:DCM and the reaction ran for 3 hours at 23 C to yield prdouct 5 (90%).
EDCl = 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, NEt3 = triethylamine, TFA= trifluoroacetic acid, DCM = dichloromethane, SEM = 2-(trimethylsilyl)ethoxymethyl, Boc = tertbutoxycarbonyl.
Glossary
Staudinger Reaction - reaching which involves the splitting of an azide (N3) group and additio of a nucleophilic group, releasing N2. A reachion mechanism is seen here (link "here" to leading question).
Boc - tertbutoxycarbonyl group (see below)______TFA - trifluoroacetic acid, a weak acid (see below)______SEM - 2-(trimethylsilyl)ethoxymethyl (see below)
__________
_____________________________________________
__________________________________
[1] Yamaguchi, J.; Seiple, I.B.; Young, I.S.;O'Malley, D.P.; Maue, M.; Baran, P.S. Angew. Chem. Int. Ed. 2008, 47, 3578-3580.
[2] Whitten, J.P.; Matthews, D.P.; McCarthy, J.R. J. Org. Chem. 1986, 51(10), 1891-1894.
____SIMBA'S __________NALA'S_______ RAFIKI'S ----__---PUMBA & TIMON'S -___-SCAR'S
Leading Questions-_____-Citations-------Experimental-------------Mechanism-------------H-NMRs