Directed reduction of .beta.-hydroxy ketones employing tetramethylammonium triacetoxyborohydride

Evans, David A.; Chapman, Kevin T.; Carreira, Erick M.

doi:10.1021/ja00219a035

Cited by 1,020 publications

(602 citation statements)

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“…This reaction, developed in these laboratories in 1992, 4 led to the formation of aldol adduct 6 in excellent diastereoselectivity. Anti-selective reduction with tetramethylammonium triacetoxyborohydride 5 formed diol 7, which was converted to aldehyde 8 in three steps. Addition of Chan's diene 9 6 mediated by BF 3 •OEt 2 gave the desired Felkin aldol adduct 10 as a single diastereomer.…”

Section: Synthesis Of the Macrolactone Fragment: 1 St Generationmentioning

confidence: 99%

“…Aldol adduct 25b was not stable to column chromatography, and was therefore subjected directly to the anti-selective reduction conditions utilized previously (Scheme 8). 5 Unfortunately, the initial product of this reaction, cyclohexylboronic ester 26, proved generally resistant to hydrolysis. Treatment of the unpurified boronic ester with diethanolamine, however, led to cleavage of the boronic ester with concomitant lactonization to form 27.…”

Section: Synthesis Of the Macrolactone Fragment: 2 Nd Generationmentioning

confidence: 99%

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Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Evans

Burch

et al. 2008

Tetrahedron

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The enantioselective total synthesis of callipeltoside A is described. Two syntheses of the macrolactone subunit are included: the first relies upon an Ireland-Claisen rearrangement to generate the trisubstituted olefin geometry and the second utilizes an enantioselective vinylogous aldol reaction for this purpose. Enantioselective syntheses of the sugar and chlorocyclopropane side chain fragments are also disclosed. The relative and absolute stereochemistry of this natural product was determined by fragment coupling with the two enantiomers of the side chain fragment.

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Section: Synthesis Of the Macrolactone Fragment: 1 St Generationmentioning

confidence: 99%

Section: Synthesis Of the Macrolactone Fragment: 2 Nd Generationmentioning

confidence: 99%

Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Evans

Burch

et al. 2008

Tetrahedron

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“…The induction was further enhanced by using (Ϫ)-Ipc 2 BCl (20) to provide 18 in 10:1 dr. † This aldol adduct proved to be a suitable substrate for hydroxyl-directed reduction, securing a 1,3-anti-relationship between C 13 and C 15 . By using Me 4 NBH(OAc) 3 (26), diol 20 was obtained cleanly (83%, Ͼ10:1 dr). The stereochemical relationship between the hydroxylbearing centers was determined by nuclear Overhauser effect analysis of the corresponding p-methoxybenzylidene acetal (see supporting information for details).…”

Section: Previous Structural Studies On the Sphinxolides And Reidispomentioning

confidence: 99%

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Paterson¹,

Britton²,

Ashton³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Reidispongiolide A is a representative member of the sphinxolide͞ reidispongiolide group of cytotoxic 26-membered macrolides of marine origin. By interacting with actin in the cell cytoskeleton, the reidispongiolides and sphinxolides are potent microfilament destabilizing agents that represent a promising mechanism of action for developing novel anticancer drugs. An aldol-based synthesis of a library of diastereomers of C 8 -C 16 and C 5 -C 16 fragments and detailed NMR comparison with a reported degradation fragment enabled a configurational assignment for a major part of the reidispongiolide macrocyclic core, thus setting a solid foundation for ongoing synthetic efforts.M arine macrolides provide a fascinating range of structural and functional diversity, which may find application inter alia as specific molecular probes for the investigation of the cytoskeleton and cell cycle events. Unique to eukaryotic cells, the actin cytoskeleton plays a critical role in the determination of cell shape, and in a variety of cellular processes, including cell motility, division, adhesion, and intracellular transportation (1). In comparison with microtubule-interacting agents (2), such as the taxanes and vinca alkaloids, the development of anticancer drugs based on selective binding to actin and disruption of microfilament assembly has attracted relatively little attention. However, recent insight into the role played by microfilaments in cell division and metastasis has highlighted the potential of certain structural classes of actin-binding natural products as useful leads for cancer chemotherapy (3).A growing family of actin-binding macrolides that disrupt microfilament organization includes the scytophycins (e.g., 1, Fig. 1), isolated from the blue-green algae Scytonema pseudohofmanni (4), aplyronines (e.g., 2), isolated from the sea hare Aplysia kurodai (5), and sphinxolides (e.g., 3, planar structure), first reported from an unidentified Pacific nudibranch (6) and later reisolated from the New Caledonian marine sponges Neosiphonia superstes and Reidispongia coreulea, along with the congeneric reidispongiolides (e.g., 4, planar structure) (7,8). A related family of trisoxazole-containing marine macrolides, typified by mycalolide A (5) and jaspisamide A (6), are also antimicrofilament agents (9). Recently, an x-ray crystal structure of the latter compound bound to actin (10) highlighted the importance of the characteristic N-vinyl formamide-containing side chain, common to all these macrolides, in determining their biological activity. Moreover, all these actin-binding macrolides inhibit the proliferation of human cancer cell lines; for example, the scytophycins and sphinxolides exhibit potent cytotoxicity against L1210 and KB cells, with IC 50 values ranging from ng͞ml to pg͞ml (9). In addition, aplyronine A shows potent antitumor activity in vivo and has potential as a clinical candidate (9). Notably, both the scytophycins and sphinxolides circumvent multidrug resistance mediated by the overexpression of P-glycoprotein...

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“…In this aldol addition the desired syn-adduct was formed as the main isomer (58%) but with only moderate diastereoselectivity (Ϸ2:1). On diastereoselective reduction with Me 4 NBH(OAc) 3 (11) and subsequent treatment with 2,2-dimethoxypropane, acetonide 12 was obtained in high yield and diastereoselectivity (91%, 93:7).…”

Section: First-generation Approachmentioning

confidence: 99%

Toward the synthesis of the carbacylic ansa antibiotic kendomycin

Mulzer

Pichlmair

Green

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The convergent synthesis of a benzofuran analog of the carbacyclic ansa compound kendomycin has been achieved by assembling three major fragments by means of epoxide opening and directed ortho lithiation. The crucial tetrahydropyran ring was formed by a highly stereoselective cationic cyclization. Analysis of all synthesized tetrahydropyran-arene compounds reveals a hindered sp 2 -sp 3 rotation, which results in rotational isomers or atropisomers affecting macrocyclization reactions. The latter could only be achieved by means of Horner-Wadsworth-Emmons olefination.O rganic compounds derived from nature have been an abundant source of drugs and drug leads and have provided a rich array of interesting synthetic targets. Among various selection criteria, novel and complex structural features combined with interesting biological activities might be the most important ones to promote a molecule to a target for natural product synthesis. Kendomycin (1), a novel streptomyces metabolite, which was presented at a meeting in 1999, consummately meets all the requirements and thus was selected as a target for our research one year later. Originally, 1 had been published as (Ϫ)-TAN 2162 in the patent literature as a potent endothelin receptor antagonist and antiosteoporotic compound (1-3). With its reisolation from a different streptomyces strain, the absolute configuration of 1 has been determined. Additionally, the biosynthetic pathway and further antibiotic and cytotoxic activities have been reported (4, 5). The structure of 1 (Fig. 1) features an aliphatic ansa chain that is attached by carbons C5 and C18 to a quinone methide core. Thus, 1 is one of the very few ansa-carbon natural products that have been isolated so far. Likewise, the quinone methide structure, which can be regarded as a 1,6-oxidation product of the corresponding benzofuran, has no precedence in natural product chemistry.Particular attention should be devoted to the fully substituted tetrahydropyran ring, which is, combined with the quinone methide, a sterically encumbered region in the molecule, possibly prone to atropisomeric phenomena. In this contribution we give a progress report on our total synthesis of kendomycin (6-8). First-Generation ApproachOur initial synthetic plan (Fig. 2) focused on a ring-closing metathesis (RCM) macrocyclization of the seco intermediates 2 or 3. It was obvious that the formation of the quinone methide chromophore should be deferred to the end of the synthesis, envisaging either an oxidation of the corresponding benzofuran or a 1,6-elimination. Key intermediates 2 and 3 were to be assembled either by a Heck coupling of alkene 4 and arylbromide 5 or an epoxide opening reaction of 5 with epoxide 6. The tetrahydropyran ring should be formed by an intramolecular hetero-Michael addition of enone 7, which should be derived from a Horner-Wadsworth-Emmons (HWE) olefination of aldehyde 8 with ␤-ketophosphonate 9.As outlined in Fig. 3, the stereotetrad of the tetrahydropyran ring was constructed by aldol addition methodology and...

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Directed reduction of .beta.-hydroxy ketones employing tetramethylammonium triacetoxyborohydride

Cited by 1,020 publications

References 0 publications

Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Toward the synthesis of the carbacylic ansa antibiotic kendomycin

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Directed reduction of .beta.-hydroxy ketones employing tetramethylammonium triacetoxyborohydride

Cited by 1,020 publications

References 0 publications

Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C 5 –C 16 degradation fragment of reidispongiolide A

Toward the synthesis of the carbacylic ansa antibiotic kendomycin

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Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A