Pederin: The Metallated Dihydropyran Approach. Stereoselective Reduction of<i>N</i>-Acylimidates<i>via</i>Rhodium-Catalysed Hydroboration

Kocieński, Philip; Jarowicki, Krzysztof; Marczak, Stanisław

doi:10.1055/s-1991-28418

Cited by 49 publications

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“…Conversion of lactone 17 to the stannane 18 was accomplished by a 3-step sequence previously described in our synthesis of Pederin. 13 Dihydropyranone 25, a critical intermediate in the synthesis of the trioxabicyclo[4.4.0]decane ring system (Scheme 3), harbours a single stereogenic centre at C-15 which was constructed efficiently by two different routes. In the first route, the lithium enolate prepared from ethyl isobutyrate was condensed with 4-chlorobutanoyl chloride to give the β-keto ester 18 in 93% yield.…”

Section: Methodsmentioning

confidence: 99%

A Synthesis of Mycalamide B

Kocieński¹,

Narquizian²,

Raubo³

et al. 1998

Synlett

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Mycalamide B, a potent antitumour agent, was synthesised from cheap, readily available starting materials: ethyl lactate, ethyl isobutyrate, 4-chlorobutanal, and 4-chlorobutanoyl chloride. The trioxabicyclo[4.4.0]decane ring system was created by reaction of a methoxymethyl ether with a silyloxyoxirane induced by phosphorus pentoxide.Mycalamides A 1 and B 2 were isolated from a sponge of the genus Mycale and shown to be potent inhibitors of tumour proliferation in a number of human tumour cell lines. 1,2 Total syntheses of mycalamides A and B have been reported by Hong and Kishi and elegant approaches to the various advanced fragments have been described by Nakata 3,4 , Roush 5,6 and Hoffmann 7,8 . We now report a synthesis of mycalamide B which shares the same fragment linkage strategy as our synthesis of 18-O-methylmycalamide B (Scheme 1). 9 However, the synthetic routes to the fragments 5 and 6 have been completely redesigned to offer greater flexibility, efficiency, and economy. Scheme 1The preparation of the 6-lithio-3,4-dihydro-2H-pyran 6 (Scheme 2) began by a diastereoselective conjugate addition of lithium dimethylcuprate to the ester 7 (Note 1) in the presence of TMSCl. The adduct 8, obtained in 95% yield, revealed a dr of >15:1. 10,11 The final C-C bond forming reaction in the sequence was also highly diastereoselective. Alkylation of the potassium enolate of the ester 8 with allyl bromide gave the third contiguous stereogenic centre in 9 in 99% yield (dr > 20 :1). Routine transformations accomplished the conversion of 9 to the alcohol 12 in preparation for the next critical step in the sequence, the inversion of configuration at C-2 (mycalamide numbering), which was plagued by competing elimination. However, the combination of trityl as the protecting group and p-chlorobenzoic acid as the nucleophile returned the nicely crystalline inverted ester 13 in 79% yield. Oxidative cleavage of the alkene followed by acid treatment achieved simultaneous trityl deprotection and lactonisation to give the second crystalline compound of the series, the lactone 15. The phenylselenide group in 16 was introduced by nucleophilic substitution of the butyrolactone. 12 Reductive cleavage of the p-chlorobenzoate in 16 (Note 2) returned a hydroxy acid which lactonised to 17 in 72% yield. Conversion of lactone 17 to the stannane 18 was accomplished by a 3-step sequence previously described in our synthesis of Pederin. 13 Dihydropyranone 25, a critical intermediate in the synthesis of the trioxabicyclo[4.4.0]decane ring system (Scheme 3), harbours a single stereogenic centre at C-15 which was constructed efficiently by two different routes. In the first route, the lithium enolate prepared from ethyl isobutyrate was condensed with 4-chlorobutanoyl chloride to give the β-keto ester 18 in 93% yield. Catalytic asymmetric hydrogenation 14-16 of the β-keto ester using [(R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] chloro (p-cymene) ruthenium chloride installed the requisite (R)-configured stereogenic centre in good yield a...

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Section: Methodsmentioning

confidence: 99%

A Synthesis of Mycalamide B

Kocieński¹,

Narquizian²,

Raubo³

et al. 1998

Synlett

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“…37 In another example, the cyclic compound shown in Equation 22 reacted cleanly with BuLi, giving the vinyllithium reagent in quantitative yield. 38 The neighboring aryl selenoether group did not present any problems in the transmetallation step. As noted earlier, a functional group that can react with alkyllithium can compete with tinlithium exchange.…”

Section: Oxygen or Sulfur Substituentsmentioning

confidence: 94%

Carbanion generation through tin-lithium exchange of vinyl-, aryl-, and hetarylstannanes

Rim¹,

Son

2006

Arkivoc

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“…SEM Protection led to 6 in 92 ± 99% yield, hydrogenation of which gave the tetrol 7 (98%). The primary-alcohol functions were protected as (tert-butyl)dimethylsilyl Scheme 4 Scheme 5 which C(8) and C(7) were attached first to the right-hand part via an amide bond, followed by subsequent elaboration of the pederic acid moiety [6] [8].…”

Section: Ethoxy]methyl)mentioning

confidence: 99%

Synthesis of Pederic Acid and Related Model Studies

Breitfelder

Schuemacher

Rölle

et al. 2004

Helvetica Chimica Acta

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{[2-(Trimethylsilyl)ethoxy]methyl} (SEM)-protected pederic acid 16 was prepared by deriving the stereogenic center at C(7) from mannitol and those at C(2) and C(3) (mycalamide numbering) from trans-2,3-dimethyloxirane. Routes to pederamides involving a late oxygenation at C(7) were explored.Introduction. ± The pederins [1], theopederins [2], mycalamides [3], and onnamides [4] are all amides of type 1 of pederic acid ( (aS,2R,5R,6R)-tetrahydroa-hydroxy-2-methoxy-5,6-dimethyl-4-methylene-2H-pyran-2-acetic acid; 2). In previous syntheses (mycalamides [5] [6], pederin [7 ± 10]) of members of these classes of compounds, the two parts of the target molecules were joined by formation of the amide bond b (cf. Eqn. 1 in Scheme 1). We were interested in a different approach [11], in which bond a is formed, requiring the right-hand building block to carry an isocyanate function. The polarity of this functional group was to be reversed by transformation to a lithiated carbamate, which should then be coupled with a norpederic acid derivative (cf. Eqn. 2). While this approach worked fine with model isocyanates [11], it failed when applied to a more elaborate isocyanate [12] that would have led to a fully functionalized mycalamide. In continuing our efforts, we wanted nevertheless to retain the approach via an isocyanate and considered forming bond b by a decarboxylative coupling of a protected pederic acid to isocyanates (cf. Eqn. 3) [13]. To apply this reaction to a synthesis of pederin or the mycalamides, we needed a reliable route to suitable protected pederic acid derivatives.Several syntheses of pederic acid and derivatives have been reported over the last 25 years [7] [14 ± 19]. Except for two syntheses [18] [19], establishment of the stereogenic center at C(7) (mycalamide numbering) required extra steps, such as oxidation to a ketone and reduction with variable stereoselectivity. Therefore, we opted to derive this stereogenic center from a chiral building block. Second, the previously used [15 ± 17] import of the stereogenic centers at C(2) and C(3) (mycalamide numbering) from enantiomerically pure trans-2,3-dimethyloxirane appeared highly advantageous. This led us to the synthons trans-2,3-dimethyloxirane, 3, and 4 (Scheme 2).We describe in the following a synthesis of the SEM-protected pederic acid 16 along these lines (SEM [2-(trimethylsilyl)ethoxy]methyl).

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Pederin: The Metallated Dihydropyran Approach. Stereoselective Reduction ofN-AcylimidatesviaRhodium-Catalysed Hydroboration

Cited by 49 publications

References 0 publications

A Synthesis of Mycalamide B

A Synthesis of Mycalamide B

Carbanion generation through tin-lithium exchange of vinyl-, aryl-, and hetarylstannanes

Synthesis of Pederic Acid and Related Model Studies

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