Alkaloids of the Aspidospermine Group

Saxton, J. E.

doi:10.1016/s0099-9598(08)60005-x

Cited by 55 publications

(30 citation statements)

References 348 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The structural diversity and the biological activity of the aspidosperma [1] family of alkaloids has attracted considerable attention from the scientific community over the past decades. [2,3] There are more than 250 natural alkaloids sharing the common pentacyclic aspidosperma core (Figure 1, rings A–E) with several distinct subfamilies possessing C21-oxygenation.…”

mentioning

confidence: 99%

“…[2,3] There are more than 250 natural alkaloids sharing the common pentacyclic aspidosperma core (Figure 1, rings A–E) with several distinct subfamilies possessing C21-oxygenation. [1] (−)-Deoxoapodine ( 1 ) was first isolated from Tabernae armeniaca in 1975, [4a] and later also found in Hazunta modesta in 1980. [4b] The hexacyclic C21-oxygenated alkaloid (−)- 1 features a distinct oxolane ring in addition to the archetypal aspidosperma pentacycle, offering a structure with four contiguous stereocenters, including the C5- and C12-quaternary stereocenters.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Enantioselective Total Synthesis of (−)‐Deoxoapodine

et al. 2017

View full text Add to dashboard Cite

The first enantioselective total synthesis of (−)-deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction for desymmetrization of an advanced intermediate that introduces the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core was accessed via an electrophilic C19-amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (−)-deoxoapodine with complete stereochemical control.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Enantioselective Total Synthesis of (−)‐Deoxoapodine

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Efficient and elegant strategies for the total synthesis of various members of this alkaloid family have been reported. 1,2 Padwa and co-workers demonstrated that the tandem cyclic carbonyl ylide formation-1,3-dipolar cycloaddition reaction 3 of diazo imides catalyzed by Rh 2 (OAc) 4 is one of the most powerful methods for the rapid construction of the pentacyclic ABCDE framework of (−)-vindoline (1) 4,5 and (−)-vindorosine (2) 6,7 (eq. 1).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Asymmetric approach to the pentacyclic skeleton of Aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates

Nambu

Hikime

Krishnamurthi

et al. 2009

Tetrahedron Letters

View full text Add to dashboard Cite

This paper describes asymmetric tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reaction of diazo imides containing a tethered indole catalyzed by chiral dirhodium(II) carboxylates as an approach to the pentacyclic skeleton of Aspidosperma alkaloids. The cycloaddition of carbonyl ylides derived from indolyl-substituted 2-diazo-5-imido-3-ketoesters under the influence of dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh 2 (S-TCPTTL) 4 , provides cycloadducts in moderate yields and enantioselectivities of up to 66% ee as well as with perfect endo diastereoselectivity. This is the first example of asymmetric induction in an intramolecular cycloaddition of a carbonyl ylide across an indolyl -bond. --------------------------------Over the past four decades, Aspidosperma alkaloids have been a source of structurally intriguing target molecules that continue to challenge the capabilities of contemporary organic synthesis. Efficient and elegant strategies for the total synthesis of various members of this alkaloid family have been reported. 1,2Padwa and co-workers demonstrated that the tandem cyclic carbonyl ylide formation-1,3-dipolar cycloaddition reaction 3 of diazo imides catalyzed by Rh 2 (OAc) 4 is one of the most powerful methods for the rapid construction of the pentacyclic ABCDE framework of (−)-vindoline (1) 4,5 and (−)-vindorosine (2) 6,7 (eq. 1). 8The same group has Corresponding author. Tel.: +81 11 706 3236; fax: +81 11 706 4981. E-mail address: hsmt@pharm.hokudai.ac.jp (S. Hashimoto).2 accomplished the total synthesis of (±)-aspidophytine 9 employing an intramolecular 1,3-dipolar cycloaddition of carbonyl ylide across the indole -bond. 10((Please Insert Eq. 1 here:))The synthetic utility of the carbonyl ylide cycloaddition strategy has also been demonstrated in its application to the synthesis of a variety of natural products. 11Over the past decade, considerable effort has been directed to the development of an enantioselective version of carbonyl ylide formation-1,3-dipolar cycloaddition catalyzed by chiral dirhodium(II) complexes. [12][13][14][15] In this process, the chiral dirhodium(II) catalyst must be capable of associating with carbonyl ylide intermediates in the cycloaddition step, because catalyst-free carbonyl ylides are achiral. Hodgson and co-workers were the first to demonstrate high levels of asymmetric induction (up to 90% ee) in intramolecular cycloadditions of carbonyl ylides derived from unsaturated -diazo--ketoesters using binaphtholphosphate catalyst Rh 2 (R-DDBNP) 4 (4) ( Figure 1).Recently, we reported catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoesters-derived carbonyl ylides with arylacetylene, alkoxyacetylene, and styrene dipolarophiles using Rh 2 (S-TCPTTL) 4 (3a), Gratifyingly, the use of benzyl ester 7c greatly improved the enantioselectivity to provide cycloadduct 6c in 50% yield with 63% ee (entry 3), whereas a low level of asymmetric induction was obtained in the reaction of 2-pheny...

show abstract

“…1 In particular, members of the Aspidosperma alkaloid family have occupied a central place in natural product chemistry because of their diverse biological activity. 2 This family of indole alkaloids contains over 250 members that share in their molecular structure a common pentacyclic ABCDE framework, with the C-ring being of critical importance because all six stereocenters and most of the functionalities are located in this ring. 3 Individual members differ mainly in functionality and stereochemistry.…”

Section: Introductionmentioning

confidence: 99%

Preparation of 2-diazo-2-oxopiperidin-3-yl-3-oxopropanoates. Useful reagents for Rh(II)-catalyzed cyclization-cycloaddition chemistry

Hong¹,

Mejía-Oneto²,

France³

et al. 2006

Arkivoc

View full text Add to dashboard Cite

2-Diazo-2-oxopiperidin-3-yl-3-oxopropanoates containing a tethered indolyl group have been identified as useful intermediates for the Rh(II)-catalyzed cyclization-cycloaddition cascade for the synthesis of the core skeleton of various aspidosperma alkaloids. Several synthetic methods were developed to rapidly construct these important diazo imide substrates using cheap and readily available reagents.

show abstract

Alkaloids of the Aspidospermine Group

Cited by 55 publications

References 348 publications

Enantioselective Total Synthesis of (−)‐Deoxoapodine

Enantioselective Total Synthesis of (−)‐Deoxoapodine

Asymmetric approach to the pentacyclic skeleton of Aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates

Preparation of 2-diazo-2-oxopiperidin-3-yl-3-oxopropanoates. Useful reagents for Rh(II)-catalyzed cyclization-cycloaddition chemistry

Contact Info

Product

Resources

About