First Total Synthesis of (+)-Pancratistatin: An Unusual Set of Problems

Tian, Xinrong; Hudlický, Tomáš; Koenigsberger, K.

doi:10.1021/ja00117a046

Cited by 150 publications

(70 citation statements)

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“…[6] The first total synthesis of racemic 1 was reported by Danishefsky and Lee in 1989, [7] and six years later Hudlicky and co-workers described the first enantioselective synthesis. [8] At present, eight different groups have reported synthetic strategies leading to 1. [7][8][9][10][11][12][13][14] Most remarkable is the synthesis by Trost and Pulley, whereby 1 is prepared in 11 % overall yield from conduritol A acetonide after only 12 steps.…”

Section: Introductionmentioning

confidence: 99%

“…[8] At present, eight different groups have reported synthetic strategies leading to 1. [7][8][9][10][11][12][13][14] Most remarkable is the synthesis by Trost and Pulley, whereby 1 is prepared in 11 % overall yield from conduritol A acetonide after only 12 steps. [9] Racemic 2 was first synthesised by Ohta and Kimoto in 1976 as an advanced intermediate in the total synthesis of another hydroxylated phenanthridone, lycoricidine.…”

Section: Introductionmentioning

confidence: 99%

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

Håkansson

Palmelund

Holm

et al. 2006

Chemistry A European J

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Håkansson

Palmelund

Holm

et al. 2006

Chemistry A European J

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“…In 1995 we published the first enantioselective synthesis 13 of this compound, previously prepared in racemic form by Danishefsky. 14 The diol derived from bromobenzene was converted to aziridine 8 and combined with the functionalized benzamide 10 to yield, in four steps, the core of the target with four of its six centers correctly installed, Scheme 2.…”

Section: Pancratistatin and 7-deoxypancratistatinmentioning

confidence: 99%

Chemoenzymatic synthesis of complex natural and unnatural products: morphine, pancratistatin, and their analogs

Hudlický¹

2006

Arkivoc

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The synthesis of morphine (1) and pancratistatin (2) have been the subject of intense effort by the synthetic community for many years. Our focus on the total synthesis of these challenging targets resulted in several generations of approaches that combine enzymatic transformations with traditional synthetic protocols in order to provide for maximum efficiency and brevity in attaining the targets.Recombinant strains that express toluene dioxygenase (TDO) are used to provide the homochiral diene cis-diol derived from bromobenzene and containing the structural features of both ring C of morphine and ring C of pancratistatin. Bromocatechol, representing ring A of morphine, is also derived from bromobenzene by fermentation with E.coli JM109 that expresses TDO as well as catechol dehydrogenase. In this fashion twelve of the carbons in morphine originate in the same starting material. One approach is based on the Kazmaier-Claisen rearrangement of glycinate esters, the other on an intramolecular Heck reaction. The route to pancratistatin and to its unnatural analogs is based on the metal-mediated cyclotrimerization of acetylenic substrates of type 3. The core of this Amaryllidaceae constituent has been attained in the initial stages of this project. The details of the synthetic endeavours toward these and other heterocyclic targets will be disclosed with emphasis on practicality, brevity, and efficiency as guiding principles of enviromentally benign manufacturing of relevant compounds.

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“…The syntheses of optically active lycoricidine (260) [280], narciclasine (261) [281], pancratistatin (264), [282], [283] and 7-deoxypancratistatin (263) [284], [285] have been reported. …”

Section: Nariclasine Typeunclassified