Formal total synthesis of (+/-)-gamma-lycorane and (+/-)-1-deoxylycorine using the [4+2]-cycloaddition/rearrangement cascade of furanyl carbamates | Health & Environmental Research Online (HERO)

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Citation
Tags

HERO ID

7417556

Reference Type

Journal Article

Title

Formal total synthesis of (+/-)-gamma-lycorane and (+/-)-1-deoxylycorine using the [4+2]-cycloaddition/rearrangement cascade of furanyl carbamates

Author(s)

Padwa, A; Brodney, MA; Lynch, SM; ,

Year

2001

Is Peer Reviewed?

Yes

Journal

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904

Publisher

AMER CHEMICAL SOC

Location

WASHINGTON

Volume

Issue

Page Numbers

1716-1724

Language

English

PMID

11262118

DOI

10.1021/jo0014109

Web of Science Id

WOS:000167403900025

URL

https://pubs.acs.org/doi/10.1021/jo0014109
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Abstract

The total syntheses of gamma-lycorane and (+/-)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu(3)SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C(2)(-)C(3)(-)C(12) allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (+/-)-1-deoxylycorine via known synthetic intermediates.

Keywords

carbamic acid derivative; deoxylycorine; lycorine; unclassified drug; analytic method; article; cell division; chemical reaction; growth inhibition; hydrolysis; proton transport; reaction analysis; stereochemistry; synthesis; X ray crystallography; Alkaloids; Amaryllidaceae Alkaloids; Carbamates; Magnetic Resonance Spectroscopy; Molecular Structure; Phenanthridines