Flexible Routes to the 5‐Hydroxy Acid Fragment of the Cryptophycins

Phukan, Prodeep; Sasmal, Sanjita; Maier, Martin E.

doi:10.1002/ejoc.200210695

Cited by 34 publications

(24 citation statements)

References 44 publications

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“…We utilized Evans aldol methodology [18] and treated (4R)-oxazolidinone 14 with propanal 7 [19][20][21] to give the syn aldol product 17 with high diastereoselectivity (d.r. > 95:5) (Scheme 4).…”

Section: Scheme 2 Retrosynthesis Of Gephyronic Acid (3)mentioning

confidence: 99%

Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid

et al. 2010

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Section: Scheme 2 Retrosynthesis Of Gephyronic Acid (3)mentioning

confidence: 99%

Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid

et al. 2010

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“…Both substances were protected with TBSOTf to give 17a and 17b. 17 The chiral auxiliary was removed by treatment with DIBAL-H in toluene to offer aldehydes 18a and 18b in yields of 85% and 72% respectively. 18…”

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confidence: 99%

A synthetic entry to pladienolide B and FD-895

Mandel

Jones

Clair

et al. 2007

Bioorganic & Medicinal Chemistry Letters

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Presented within are syntheses of the pladienolide B and FD-895 side-chains, as well as models of the essential ring-closing metathesis and Stille coupling that will be used to complete the total synthesis of both products. Several analogs of the pladienolide B side-chain were also prepared in order to evaluate the scope of the methodology and to create a library of structures that could be used for stereochemical and SAR analyses.The pladienolides (1a-1g) are a set of highly bioactive macrocyclic polyketides isolated from an Okinawan strain of Streptomyces platensis ( Figure 1). 1 Previously, FD-895 (1h) was reported in 1994 from an isolate of Streptomyces hygroscopicus. 2 This family of macrolides (1a-1h) displays potent anti-proliferative and tumor suppressive activity when assayed in both cell culture and xenograft models. 2a,c Several members of the family, including pladienolide B (1b), inhibited tumor cell growth at low nanomolar concentrations. Subsequent cell cycle studies indicate that 1b blocks cell growth in both the G1 and the G2/M phase, suggesting a unique mode of action. In addition, pladienolide B (1b) has been shown to deliver potent tumor regression and inhibition of mouse xenografts.At the beginning of our studies, only the two dimensional structures of 1a-1h were known. This combined with lack of access to the compounds themselves or their producer strains meant that we would have to determine the stereochemistry de novo. 4 Given recent advances in NMR techniques and the use of libraries to elucidate the three dimensional configuration of natural products, 5 we felt that this study would provide an ideal platform to use chemical synthesis in concert with more traditional methods to determine the stereochemistry of these macrolides. 6 Moreover, the required general approaches to the stereochemistry of 1b and 1h are synthetic strategies that allow access to many analogs for future research on these promising lead compounds. In parallel, the methods developed in this research serve as a prelude to the total synthesis of the pladienolides and FD-895. 7Our general retrosynthetic analysis (Scheme 1) of the family began by visualizing a convergent union at the diene by a Stille coupling of side-chain 2 to core 3. Stannane 2 was ideal because conditions for tin insertion do not cause side reactions with the epoxide. 8 Stannane 2 could then be derived from alcohol 4 that would result from epoxidation of olefin 5 using a suitable method. 9 Olefin 5 would follow naturally from a Julia-Kociensky reaction of aldehyde 6 and sulfone 7. 10 Macrolide 3 would then be derived from a ring-closing metathesis of 8. In turn, 8 could be prepared by coupling of alcohol 9 and carboxylic acid 10. This two step ester formation -RCM has precedent in our laboratory. 11 As this article was being prepared, Kotake has indeed shown that this disconnection can be used to assemble pladienolide B (1b) and D (1d). 3With a synthetic plan in hand, we turned to evaluate the complexity of the proposed synthetic endeavor. Wit...

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“…On the other hand, when the reaction was performed using a 1 (1.3 mmol)/2a ratio of 1:1o ra ll the DHA was added in 1s tep, the yield of 3a based on 1 was reduced by half (Table 1, entries 3and 4). We subsequently investigated the influence of the counter-anion of the Sn halideso n the formationo fe ach product, by conducting experiments with anhydrous SnBr 2 ,S nBr 4 ,S nI 2 ,a nd SnI 4 (Table 1, entries [5][6][7][8]. The use of SnBr 2 gave unsatisfactory product yields, similar to those observed with SnCl 2 ·2 H 2 O( Ta ble 1, compare entry 1), while the yield of 3a decreased even furtherw hen SnBr 4 was employed (Table 1, entries 5a nd 6).…”

Section: Resultsmentioning

confidence: 99%

“…Mosto ft he previous reports on chemical [3] or enzymatic [4] syntheses of fivemembered lactones are based on multistep processes, and, therefore, the developmento famore efficient and aw idely applicable approachw ith an inexpensive and easily available startingm aterial is extremely significant in the field of ag reen and sustainable chemistry.O nt he other hand, we previously reportedt he catalytic transformation of at riose sugar (1,3-di-hydroxyacetone, DHA)a nd formaldehyde into a-hydroxy-g-butyrolactone (HBL), one of the most important intermediates in pharmaceutical synthesis. [5][6][7][8] Among different Lewis acid catalysts examined, tin chlorides exhibited the best performancei n the above reaction. The cascade transformationi nvolves four steps:i )isomerization andd ehydration of DHA to pyruvic aldehyde (PA), ii)aldol reactionb etween PA and formaldehyde, iii) formation of the five-membered ring, and iv) protont ransfer to form HBL (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Cascade Synthesis of Five‐Membered Lactones using Biomass‐Derived Sugars as Carbon Nucleophiles

Yamaguchi

Matsuo

Motokura

et al. 2016

Chemistry An Asian Journal

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We report the cascade synthesis of five-membered lactones from a biomass-derived triose sugar, 1,3-dihydroxyacetone, and various aldehydes. This achievement provides a new synthetic strategy to generate a wide range of valuable compounds from a single biomass-derived sugar. Among several examined Lewis acid catalysts, homogeneous tin chloride catalysts exhibited the best performance to form carbon-carbon bonds. The scope and limitations of the synthesis of five-membered lactones using aldehyde compounds are investigated. The cascade reaction led to high product selectivity as well as diastereoselectivity, and the mechanism leading to the diastereoselectivity was discussed based on isomerization experiments and density functional theory (DFT) calculations. The present results are expected to support new approaches for the efficient utilization of biomass-derived sugars.

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Flexible Routes to the 5‐Hydroxy Acid Fragment of the Cryptophycins

Cited by 34 publications

References 44 publications

Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid

Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid

A synthetic entry to pladienolide B and FD-895

Cascade Synthesis of Five‐Membered Lactones using Biomass‐Derived Sugars as Carbon Nucleophiles

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