A total synthesis of (+)-negamycin through isoxazolidine allylation

Bates, Roderick W.; Khanizeman, Rab'iah Nisha; Hirao, Hajime; Tay, Yu Shan; Sae‐Lao, Patcharaporn

doi:10.1039/c4ob00537f

Cited by 22 publications

(8 citation statements)

References 36 publications

(6 reference statements)

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“…80 An interesting variant of the N-acyliminium allylation reaction was investigated during the synthesis of (+)-negamycin, a microbial antibiotic from Streptomyces purpeofuscus (Scheme 8d). 81 In the presence of allyltrimethylsilane and boron trifluoride etherate at −40 °C, 3-methoxyisooxazolidine 8-13 afforded trans-8-14 in 88% yield. This product encoded the full stereochemistry of (+)-negamycin, which was prepared in three additional steps.…”

Section: Chemical Reviewsmentioning

confidence: 99%

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

et al. 2016

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The main objective of this review is to provide a comprehensive survey of methods used for stereoselective construction of carbon-nitrogen bonds during the total synthesis of nitrogen-containing natural products that have appeared in the literature since 2000. The material is organized by specific reaction in order of decreasing number of applications in natural product synthesis. About 800 total syntheses of natural products with stereogenic carbon-nitrogen bonds described since 2000 have been reviewed.

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Section: Chemical Reviewsmentioning

confidence: 99%

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

et al. 2016

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“…14 Remarkably, when the side chain was a chloromethyl group, a single isomer was formed, allowing a highly stereoselctive synthesis of negamycin 38. 15 Scheme 8. Access to trans-substituted isoxazolidines Another neglected group of sedum alkaloids are those that have an oxygen substituent on the piperidine ring.…”

Section: Scheme 7 a Synthesis Of Sedininementioning

confidence: 99%

Synthesis of the sedum and related alkaloids: A personal perspective

Bates

2018

Tetrahedron Letters

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“…In more recent work carried out by another group member, Nisha Khanizeman, we were pleasantly surprised to find that the allylation of chlorine substituted isoxazolidine 3-112 under the same conditions gave the desired trans isomer 3-113 as a single isomer. 237 This ultimately led to the total synthesis of (+)-negamycin.…”

Section: Scheme 34-2 Retrosynthetic Strategy (Pathway A)mentioning

confidence: 99%

“…Lowest energy conformations of iminium ion intermediate with chloro and ethyl substituents Scheme 3.4-7 Conversion of hydroxymethyl to chloromethyl isoxazolidineThe hypothesis was then extended to include other electronegative functional groups and as such, hydroxymethyl isoxazolidine 3-114 was prepared 237. Treatment of 3-114 with allyltrimethylsilane under the same conditions as the conversion from 3-112 to 3-113, gave the trans-isoxazolidine 3-115 as a single isomer.…”

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confidence: 99%

Synthesis of piperidine and quinolizidine alkaloids

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Natural products have been, and will continue to be, an important starting point for researchers in the quest for novel treatments for today's ailments. While these molecules often have very highly potent or specialised activities, they may not be the perfect drug candidate. Medicinal chemists aim to improve their therapeutic activity and at the same 6 1-11 to give a rather low diastereomeric mixture (2.3:1) of alcohols 1-12 and 1-13 which were separable by silica gel chromatography. Acetonide cleavage of 1-12 by treatment with aqueous HCl followed by the key intramolecular cyclisation step under Mitsunobu conditions furnished pyridinium salt 1-14. Subsequent reduction with hydrogen in the presence of PtO 2 as catalyst produced a 0.8:1 mixture of diastereomers. Subsequent treatment of each diastereomer with concentrated aqueous KOH yielded (-)-lentiginosine, ent-1-1, and its 8a-epimer, 1-15. 1-epi-lentiginosine, 1-16, was also synthesised in a similar fashion. Preparation of the 1-epimer began with alcohol 1-13 and the reduction step proceeded with high yields and diastereoselectivity. Scheme 1.2-2 Fruit's synthesis of (-)-lentiginosine, analogues 1-15 and 1-16 Brandi and co-workers also used a pyridine-based strategy to synthesise racemic lentiginosine (Scheme 1.2-3). 16 Here, pyridyl alcohol 1-17 was identified as a good starting point. Brandi reasoned that the double bond present could undergo electrophilic addition and then cyclise to form the bicyclic skeleton. Bromination of pyridyl alcohol 1-17 with NBS in aqueous THF furnished pyridinium salt 1-18 diastereoselectively with a yield of 53%. Similar to Fruit's work, the pyridinium salt was reduced by hydrogenation with catalytic amounts of PtO 2 to furnish a 0.7:1 mixture of diastereomers 1-19a and 1-19b. The group demonstrated that the presence of a good leaving group i.e. bromine, enabled facile

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A total synthesis of (+)-negamycin through isoxazolidine allylation

Cited by 22 publications

References 36 publications

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

Cutting-Edge and Time-Honored Strategies for Stereoselective Construction of C–N Bonds in Total Synthesis

Synthesis of the sedum and related alkaloids: A personal perspective

Synthesis of piperidine and quinolizidine alkaloids

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