A divergent approach to the myriaporones and tedanolide: Enantioselective preparation of the common intermediate

Taylor, Richard E.; Ciavarri, Jeffrey P.; Hearn, Brian R.

doi:10.1016/s0040-4039(98)02110-8

“…In the synthesis of Myriaporone, Taylor et al found that external Lewis acids influenced the stereoselectivity of Zrallylation processes. 31 When epoxyaldehyde was pre-treated with magnesium bromide, subsequent Zr-allylation afforded a single diastereomeric addition product, namely the anti,synhydroxypropionate in 70% yield (Scheme 32). The preference to syn-1,2-stereochemistry was rationalized by proposing an acyclic transition state where the external Lewis acids obviated the need for internal Zr-activation of the aldehyde.…”

Section: Cooperation Of La With Tm To Increase the Selectivitymentioning

confidence: 99%

Co-operative effect of Lewis acids with transition metals for organic synthesis

Wang

¹

,

Xi

²

2007

View full text Add to dashboard Cite

Transition metal-mediated or -catalyzed carbon-carbon bond or carbon-heteroatom bond forming reactions are among the most powerful tools in organic synthesis. In addition, Lewis acid-mediated or -catalyzed organic transformations are widely used. In this context, an effective combination of these two powerful protocols or an efficient cooperation of transition metals with Lewis acids should open a new era in synthetic chemistry. This tutorial review summarizes representative synthetic methodologies developed in the past decades employing this co-operative effect.

show abstract

“…Recently, we reported the completion of the carbon skeleton of myriaporone 1 ( 2 a ) through a stereoselective homoallenylboration and a nitrile oxide cycloaddition 5a. Construction of myriaporone 4 ( 2 d ) began with known alcohol 3 3c (Scheme ). Oxidation with IBX6 was followed by an Evans aldol7 reaction to set the C8 and C9 stereocenters in high yield and excellent diastereoselectivity.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis and Stereochemical Assignment of Myriaporones 1, 3, and 4

Fleming

¹

,

Taylor

²

2004

Self Cite

View full text Add to dashboard Cite

The natural products tedanolide (1 a) and 13-deoxytedanolide (1 b), which were isolated by Schmitz et al. [1] and Fusetani et al., [2] respectively, exhibit picomolar activity against a range of cancer cell lines. Their biological activity coupled with their scarcity has prompted considerable synthetic attention.[3] Our interest in these compounds stems from the isolation of a related class of natural products, the myriaporones (2 a-d), reported by Rinehart et al. in 1995. [4, 5] The myriaporones are nearly identical structurally to the C10-C23 portion of tedanolide (1 a); it is therefore possible that these two classes of compounds share the same biological receptor and have similar modes of action. As a result of their limited availability, the biology of both classes remains a mystery. Therefore, our goal is to provide material to facilitate such studies and, herein, we report the total synthesis of myriaporones 1, 3, and 4 (2 a, c, d) and the unambiguous assignment of their previously undetermined stereogenic configurations at C5 and C6.Recently, we reported the completion of the carbon skeleton of myriaporone 1 (2 a) through a stereoselective homoallenylboration and a nitrile oxide cycloaddition.[5a]Construction of myriaporone 4 (2 d) began with known alcohol 3[3c] (Scheme 1). Oxidation with IBX [6] was followed by an Evans aldol [7] reaction to set the C8 and C9 stereocenters in high yield and excellent diastereoselectivity. During the course of that work, incorporation of the epoxide at an early stage limited the scope of reaction conditions that subsequent intermediates could withstand and ultimately prevented completion of the total synthesis. Since then, Loh and Feng [3g] and Smith III et al. [3k] reported highly selective late-stage epoxidations in their efforts toward tedanolide. With these results as precedence, our focus switched to the incorporation of this particularly sensitive functional group in the penultimate step of the synthesis. Scheme 1. Synthesis of C5-epimeric isoxazolines 9 a and 9 b. Reagents and conditions: a) IBX, 95 %; b) Bu 2 BOTf, Et 3 N, 93 %; c) TBSOTf, 85 %; d) LiBH 4 ; e) TBSCl, 89 % (two steps); f) OsO 4 , NMO, 95 %; g) NaIO 4 , 84%; h) Bu 2 BOTf, Et 3 N, 99 %; i) LiBH 4 ; j) TBSCl, 92 % (two steps); k) PrNO 2 , PhNCO, 64 %; l) DDQ, 88 %; m) IBX; n) Ph 3 P= CHCH 3 , 63 % (two steps). IBX = o-iodoxybenzoic acid; Tf = trifluoromethanesulfonyl; TBS = tert-butyldimethylsilyl; NMO = N-methylmorpholine-N-oxide; DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

show abstract

“…Recently, we reported the completion of the carbon skeleton of myriaporone 1 ( 2 a ) through a stereoselective homoallenylboration and a nitrile oxide cycloaddition 5a. Construction of myriaporone 4 ( 2 d ) began with known alcohol 3 3c (Scheme ). Oxidation with IBX6 was followed by an Evans aldol7 reaction to set the C8 and C9 stereocenters in high yield and excellent diastereoselectivity.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis and Stereochemical Assignment of Myriaporones 1, 3, and 4

Fleming

¹

,

Taylor

²

2004

Self Cite

View full text Add to dashboard Cite

The natural products tedanolide (1 a) and 13-deoxytedanolide (1 b), which were isolated by Schmitz et al. [1] and Fusetani et al., [2] respectively, exhibit picomolar activity against a range of cancer cell lines. Their biological activity coupled with their scarcity has prompted considerable synthetic attention.[3] Our interest in these compounds stems from the isolation of a related class of natural products, the myriaporones (2 a-d), reported by Rinehart et al. in 1995. [4, 5] The myriaporones are nearly identical structurally to the C10-C23 portion of tedanolide (1 a); it is therefore possible that these two classes of compounds share the same biological receptor and have similar modes of action. As a result of their limited availability, the biology of both classes remains a mystery. Therefore, our goal is to provide material to facilitate such studies and, herein, we report the total synthesis of myriaporones 1, 3, and 4 (2 a, c, d) and the unambiguous assignment of their previously undetermined stereogenic configurations at C5 and C6.Recently, we reported the completion of the carbon skeleton of myriaporone 1 (2 a) through a stereoselective homoallenylboration and a nitrile oxide cycloaddition.[5a]Construction of myriaporone 4 (2 d) began with known alcohol 3[3c] (Scheme 1). Oxidation with IBX [6] was followed by an Evans aldol [7] reaction to set the C8 and C9 stereocenters in high yield and excellent diastereoselectivity. During the course of that work, incorporation of the epoxide at an early stage limited the scope of reaction conditions that subsequent intermediates could withstand and ultimately prevented completion of the total synthesis. Since then, Loh and Feng [3g] and Smith III et al. [3k] reported highly selective late-stage epoxidations in their efforts toward tedanolide. With these results as precedence, our focus switched to the incorporation of this particularly sensitive functional group in the penultimate step of the synthesis. Scheme 1. Synthesis of C5-epimeric isoxazolines 9 a and 9 b. Reagents and conditions: a) IBX, 95 %; b) Bu 2 BOTf, Et 3 N, 93 %; c) TBSOTf, 85 %; d) LiBH 4 ; e) TBSCl, 89 % (two steps); f) OsO 4 , NMO, 95 %; g) NaIO 4 , 84%; h) Bu 2 BOTf, Et 3 N, 99 %; i) LiBH 4 ; j) TBSCl, 92 % (two steps); k) PrNO 2 , PhNCO, 64 %; l) DDQ, 88 %; m) IBX; n) Ph 3 P= CHCH 3 , 63 % (two steps). IBX = o-iodoxybenzoic acid; Tf = trifluoromethanesulfonyl; TBS = tert-butyldimethylsilyl; NMO = N-methylmorpholine-N-oxide; DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.

show abstract

A divergent approach to the myriaporones and tedanolide: Enantioselective preparation of the common intermediate

Cited by 47 publications

References 16 publications

Co-operative effect of Lewis acids with transition metals for organic synthesis

Co-operative effect of Lewis acids with transition metals for organic synthesis

Total Synthesis and Stereochemical Assignment of Myriaporones 1, 3, and 4

Total Synthesis and Stereochemical Assignment of Myriaporones 1, 3, and 4

Contact Info

Product

Resources

About