Synthesis of 7‐Deoxypancratistatin from Carbohydrates by the Use of Olefin Metathesis

Abstract

The stereocontrolled synthesis of (+)-7-deoxypancratistatin is described. The convergent synthesis has been achieved by two different strategies, both of which commence from a pentose and piperonal. The latter is converted into allylic bromide 7, which is then coupled with a protected methyl 5-deoxy-5-iodo-D-ribofuranoside in the presence of zinc metal. The first strategy involves a total of only 13 steps from D-ribose and piperonal, but suffers from a low yield in the zinc-mediated reaction between ribofuranoside 9, benzylamine, and bromide 7. The second strategy involves a total of 18 steps from D-xylose and piperonal. The former is converted into ribofuranoside 28, which is coupled with bromide 7 in the presence of zinc, and this is followed by ring-closing olefin metathesis. Subsequent Overman rearrangement, dihydroxylation, and deprotection then affords the natural product.

Synthesis of Calystegine A3 from Glucose by the Use of Ring‐Closing Metathesis

“…Reactions were monitored by TLC using aluminium plates precoated with silica gel 60. Compounds were visualized by dipping in a solution of (NH 4 ) 6 = 67.19 ppm) served as the internal standards in 13 C NMR spectroscopy. Only the major rotamer is reported in the 13 C NMR of Cbz-protected amines.…”

“…Compounds were visualized by dipping in a solution of (NH 4 ) 6 = 67.19 ppm) served as the internal standards in 13 C NMR spectroscopy. Only the major rotamer is reported in the 13 C NMR of Cbz-protected amines. High resolution mass spectra were recorded at the Department of Physics and Chemistry, University of Southern Denmark.…”

“…The resulting diene C is subsequently cyclized by olefin metathesis to generate the seven-membered carbon skeleton in the calystegines. Recently, we have also used this sequence for preparation of other carbocyclic natural products from carbohydrates including cyclophellitol, [12] 7-deoxypancratistatin [13] and gabosine A and N. [14] Scheme 2. Calystegine retrosynthesis.…”

Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives

“…[24] Thephenolic functionality in 6 was protected as its benzyl ether while the allylic bromide moiety was introduced by as equence of reactions involving Heck coupling [25] with acrylic acid, conversion of carboxylic acid to its anhydride,reduction of the anhydride to an alcohol, and finally,d isplacement of the allylic mesylate with LiBr to produce ester 7.T he authors stated that the Heck coupling proceeded only in moderate yields in the presence of triphenylphosphine;w hen the coupling was carried out under phosphine-free conditions near quantitative yields were achieved. [24] Thephenolic functionality in 6 was protected as its benzyl ether while the allylic bromide moiety was introduced by as equence of reactions involving Heck coupling [25] with acrylic acid, conversion of carboxylic acid to its anhydride,reduction of the anhydride to an alcohol, and finally,d isplacement of the allylic mesylate with LiBr to produce ester 7.T he authors stated that the Heck coupling proceeded only in moderate yields in the presence of triphenylphosphine;w hen the coupling was carried out under phosphine-free conditions near quantitative yields were achieved.…”

Moynihan Prize 01–06

“…The α,ω‐diene thus obtained is subsequently converted into the corresponding carbocycle by ring‐closing metathesis. We and others have used the combination of these organometallic reactions to prepare several carbocyclic natural products from carbohydrates including the calystegines,15 the gabosines,16 cyclophellitol17 and 7‐deoxypancratistatin 18…”