2019
DOI: 10.1038/s41467-019-10398-4
|View full text |Cite
|
Sign up to set email alerts
|

Enantioselective synthesis of cis-hydrobenzofurans bearing all-carbon quaternary stereocenters and application to total synthesis of (‒)-morphine

Abstract: (‒)-Morphine, which is selected as an essential medicine by World Health Organization, is widely applied in the treatment of the pain-related diseases. Due to its synthetically challenging molecular architecture and important clinical role, extensive synthetic studies of morphine-type alkaloids have been conducted. However, catalytic asymmetric total synthesis of (‒)-morphine remains a long-standing challenge. Here, we disclose an efficient enantioselective total synthesis of (‒)-morphine in a longest linear s… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1

Citation Types

1
19
0

Year Published

2019
2019
2023
2023

Publication Types

Select...
6
1

Relationship

1
6

Authors

Journals

citations
Cited by 65 publications
(20 citation statements)
references
References 50 publications
(44 reference statements)
1
19
0
Order By: Relevance
“…(4aS,6R,8aR)-6-Hydroxy- 3-methoxy-11-methyl-4a,5,7,8,11,12hexahydro-6H-benzo[2,3]benzofuro [4,3-cd]azepin-10(9H)-one (16). To a stirred solution of 15 (157 mg, 0.388 mmol, 1 equiv) in dry DCE (15 mL), paraformaldehyde (47 mg, 1.55 mmol, 4 equiv) and CF 3 CO 2 H (434 μL, 5.82 mmol, 15 equiv) were added sequentially at room temperature.…”
Section: ■ Experimental Sectionmentioning
confidence: 99%
See 3 more Smart Citations
“…(4aS,6R,8aR)-6-Hydroxy- 3-methoxy-11-methyl-4a,5,7,8,11,12hexahydro-6H-benzo[2,3]benzofuro [4,3-cd]azepin-10(9H)-one (16). To a stirred solution of 15 (157 mg, 0.388 mmol, 1 equiv) in dry DCE (15 mL), paraformaldehyde (47 mg, 1.55 mmol, 4 equiv) and CF 3 CO 2 H (434 μL, 5.82 mmol, 15 equiv) were added sequentially at room temperature.…”
Section: ■ Experimental Sectionmentioning
confidence: 99%
“…The D ring of target molecules 1a and 1b could be installed by an intramolecular Pictet−Spengler cyclization of intermediate I, whereas the amide moiety in I would be introduced from the common advanced building block II by a subsequent selective debenzylation/oxidation/radical-induced amidation procedure. We expected that intermediate II could be prepared via a series of functional group conversions from α,β-unsaturated ketone 2, which can be easily accessed from compound 3 via our newly developed SPD-catalyzed asymmetric Robinson annulation 16 with an excellent enantioselectivity (>99% ee). Similarly, following the above-mentioned research results, the enone precursor 3 can also be efficiently synthesized from commercially available 4 and 5 at a gram scale in just four steps.…”
mentioning
confidence: 99%
See 2 more Smart Citations
“…Second, synthetic biologists have recently achieved the complete biosynthesis of thebaine and derivatives in yeast, which, however, is far from practical application. Moreover, synthetic chemists have developed over 30 total syntheses of morphine and congeners, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] but none of these de novo approaches, especially those to oxycodone (3) [18][19][20][21][22] and related derivatives 4-7, are competitive in cost with the current farming/isolation/semisynthesis protocol. An important solution to the practical synthesis of opioids would be to mimic the methods employed by the Mother Nature.…”
Section: Introductionmentioning
confidence: 99%