Sulfoximine-mediated resolutions of ketones

Johnson, Carl R.; Zeller, James R.

doi:10.1021/ja00378a048

Cited by 69 publications

(29 citation statements)

References 2 publications

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“…After 3 h at ambient temperature, the mixture was diluted with water and extracted with ether. The ethereal extract was successively washed with water and saturated brine, dried over anhydrous (5). To a solution of LDA (prepared from 2.5 ml of diisopropylamine and 10ml of 1.551\1 methyllithium) in THF, octalone 4 (500 mg, 3 mmol) in dry THF (10 ml) was added dropwise at -78C under nitrogen.…”

Section: Methodsmentioning

confidence: 99%

“…4 ) Optical purity was evaluated by comparing the specific rotation value with that in the literature. 5) After deprotonating with LOA (lithium diisopropylamide), octalone 4 was coupled with freshly distilled acetaldehyde to give alcohol 5 as a diastereomeric mixture in an 83% yield. Successive Jones oxidation, NBS (N-bromosuccinimide) bromination, and HBr elimination with OBU (l,8-diazabicyc10[5.4.0Jun-dec-7-ene) gave diene-dione 6 in a 9% yield from 5.…”

mentioning

confidence: 99%

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Synthesis of the 5-Demethyl-6-deoxy Analogue of Sporogen AO-1, a Sporogenic Substance ofAspergillus oryzae

Tamogami¹,

Katayama²,

Marumo³

et al. 1996

Bioscience, Biotechnology, and Biochemistry

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis of the 5-Demethyl-6-deoxy Analogue of Sporogen AO-1, a Sporogenic Substance ofAspergillus oryzae

Tamogami¹,

Katayama²,

Marumo³

et al. 1996

Bioscience, Biotechnology, and Biochemistry

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“…5,6) The absolute stereochemistry of both enantiomers of 2b was then established by X-ray crystallographic analysis of 7b and 9b 7) (Chart 2). We envisaged the resolution of benzyl-protected 2a, the synthetic intermediate of racemic akaterpin, 8) would also be possible as 2b.…”

Section: 3)mentioning

confidence: 99%

Determination of the Absolute Structure of (+)-Akaterpin

Hosoi

Kawai

Hagiwara

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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We describe the total synthesis and structural determination of ( )-akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include the resolution of β,γ-unsaturated ketone ( )-2a with chiral sulfoximine 6. The absolute stereochemistry was determined by comparison of the specific optical rotation data of ( )-1 and ( )-1 with that of natural akaterpin.Key words total synthesis; absolute stereochemistry; optical resolution Umezawa and co-workers originally isolated akaterpin (1) from the marine sponge Callyspongia sp. as an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC).1) PI-PLC triggers phosphatidylinositol turnover by hydrolyzing phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into diacylglycerol (DG) and 1,4,5-trisphosphate (IP 3 ). Thus, a specific PI-PLC inhibitor is considered a promising anti-tumor candidate and a valuable tool for the investigation of signal transduction. 2,3)Until recently the precise structure of akaterpin had not been determined because of difficulties in isolating this compound from the natural source. We have been investigating a synthetic study of akaterpin and recently reported the relative stereochemistry of the compound by synthesizing possible isomers in racemic form and comparing the corresponding spectral data with those of the authentic natural product.4) Herein we describe the determination of the absolute stereochemistry of (+)-akaterpin. Our approach was to synthesize optically active akaterpin by resolution of the key intermediate in the racemic synthesis. We reasoned that β,γ-unsaturated ketone 2a was suitable for this purpose. Having resolved the key intermediate 2a, each enantiomer was then separately transformed to akaterpin following the same synthetic procedure as used for the racemate.In this regard, we previously reported the successful resolution of methyl-protected 2b by using chiral sulfoximine 6, which was developed by Johnson. 5,6) The absolute stereochemistry of both enantiomers of 2b was then established by X-ray crystallographic analysis of 7b and 9b 7) (Chart 2). We envisaged the resolution of benzyl-protected 2a, the synthetic intermediate of racemic akaterpin, 8) would also be possible as 2b. Thus, both enantiomers of akaterpin could be synthesized

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“…lithium (R,R)-bis(α-phenylethyl)amide [14] suggested the possibility of a similar reaction of 4 and, thus, its selective Asymmetric Olefination and Synthesis of the Allylic Sulfoximine conversion to 3. Enolate 3 should allow for the stereoselective introduction of the ω-side chain in two steps via an Reaction of ketone 7 with lithiosulfoximine 8 [19] , which was prepared from readily available (R)-N,S-dimethyl-Saldol reaction with (E)-2-octenal and a Pd-catalyzed transposition of the allylic hydroxy group in the aldol from C-phenylsulfoximine [20] , in THF at Ϫ78°C gave the lithium alkoxide 9, which was not isolated but consecutively treated 13 to C-15 [15] . We have successfully applied such a sequence in asymmetric syntheses of 3-oxacarbacyclin and 3-oxaiso-with ClSiMe 3 and nBuLi to afford, after chromatography, the vinylic sulfoximine 6 (Ն98% de) in 86% yield and the carbacyclin [10c] .…”

Section: Retrosynthetic Analysismentioning

confidence: 99%

“…Ϫ IR (neat): ν ϭ 3475 (w, br), 3aͰ ,6aͰ ] } -5- 3,3a,6,6a-tetrahydro-3-(1-hydroxy-2-octenyl (2), 311 (9), 253 (2), yellow solution was formed. After stirring the solution for 2 h at 249 (2), 239 (2), 233 (2), 201 (4), 200 (11), 199 (66), 173 (34), 145 Ϫ100°C, it was cooled to Ϫ108°C and treated dropwise under film (10), 139 (19) ,2,3,3a,4,6a-hexahydro-3-(1-hydroxy-2-octenyl 19.23 (u), 22.51 (u), 25.68 (u), 26.88 (d), 27.44 (u), with saturated aqueous NH 4 Cl and warmed to room temperature. The aqueous phase was extracted with ether.…”

Section: (±)-[3јaͱ5јz(s*)6јaͱ]-n-methyl-s-phenyl-s-[{tetra-mentioning

confidence: 99%