Synthese optisch aktiver 2‐Methyl‐ und 2‐Äthyl‐1, 6‐dioxaspiro [4.4]‐nonan‐ und ‐[4.5]decan‐Pheromone aus einem gemeinsamen chiralen Vorläufer

Hungerbühler, Ernst; Naef, Reto; Wasmuth, Daniel; Seebàch, Dieter; Loosli, Hans‐Rudolf; Wehrli, A.

doi:10.1002/hlca.19800630724

Cited by 54 publications

(6 citation statements)

References 31 publications

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“…The product is purified by column chromatography on silica gel using CH 2 Cl 2 /MeOH/NH 3 (14) Citramalic acid (3 g, 20.25 mmol) was dissolved in100 ml methanol and 5 ml concentrated sulphuric acid were added. The mixture was stirred at room temperature and monitored by tlc until the total consumption of the reagent (around 48 h).…”

Section: (S)-n-benzyl-3-hydroxypyrrolidine (1a)mentioning

confidence: 99%

Approach to a better understanding and modelling of β-pyrrolidinoalcohol ligands for enantioselective alkylation

Gonsalves

Serra

Murtinho

2006

Journal of Molecular Catalysis A: Chemical

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Section: (S)-n-benzyl-3-hydroxypyrrolidine (1a)mentioning

confidence: 99%

Approach to a better understanding and modelling of β-pyrrolidinoalcohol ligands for enantioselective alkylation

Gonsalves

Serra

Murtinho

2006

Journal of Molecular Catalysis A: Chemical

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“…After several trials, 7 could be prepared in 70% yield using a combination of n-BuLi-t-BuONa as the base. 12 Dethioacetalization of 7 in the presence of HgCl 2 13 followed by acidic work-up directly produced the target spiro compound (S,S)-II via concomitant deprotection of the acetal group (Scheme 1). Cyclization of the intermediate tetrol, with identical configuration at positions 2 and 8 is known 9a,14 to furnish the 6,6-spiroketals with E,E stereochemistry.…”

Section: Synthesis Of (Ss)-spiket IImentioning

confidence: 99%

“…Cyclization of the intermediate tetrol, with identical configuration at positions 2 and 8 is known 9a,14 to furnish the 6,6-spiroketals with E,E stereochemistry. Hence, the synthesized compound would be the C 2 -symmetric (2S,6S,8S)-II, which is also reflected from its 13 C NMR resonances.…”

Section: Synthesis Of (Ss)-spiket IImentioning

confidence: 99%

Enantiomeric Synthesis of the SPIKET-P Enantiomers

Sharma¹,

Iyer²,

Gamre³

et al. 2004

Synthesis

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A convenient synthesis of the antipodes of the title compound has been developed starting from (R)-1,2,5,6-dicyclohexylidene mannitol. Some of the key features of the syntheses were simple reaction protocols, and stereoselective inversion of chiral 1,2-diol moiety via neighbouring group assisted acetylation.Microtubules that are formed by the self-association of the a,b-tubulin heterodimers play a crucial role in cell division. 1,2 Thus, compounds that can prevent polymerization of tubulin are potential anticancer agents, and have attracted recent attention. The macrocyclic spiroketal lactone, spongistatin 1 (I) is one such compound that has been isolated from an Eastern Indian Ocean sponge in the genus Hytrios. 3,4 It shows impressive cytotoxicity against the members of the NCI panel of 60 human cancer cell lines. 3 Based on molecular simulation studies on its binding interaction with tubulin, the simple spiroketal, SPIKET-P (II) has been rationally designed as the pharmacophore of spongistatin 1. 5 At nanomolar concentrations, compound II showed promising cytotoxicity against human breast cancer cells by destroying microtubule organization and inducing apoptosis. 6 The 1,7-dioxaspiro[5.5]undecane moiety present in II also constitutes the core structural unit in various natural products of biological interests. 3,7 Further, in view of conformational rigidity and thermodynamic stability, these types of functionalized spiroketals are versatile intermediates in stereoselective syntheses of complex natural products. 8 In view of the medicinal importance and the impressive performance of II as an anticancer agent, a need to develop synthesis of its enantiomers, especially from easily accessible materials, was felt. Availability of its enantiomers would facilitate studies on the stereochemical effect of the biological activity. Consequently, we have developed a convenient synthesis of both (R,R)-and (S,S)-II from the abundant and inexpensive D-mannitol. Herein, we report the results. Earlier three syntheses of II have been reported. Of these, the synthesis 9a of the enantiomers of II via Sharpless asymmetric dihydroxylation is by far the best in terms of its brevity and efficiency. However, the chemicals/reagents used in this approach are either expensive or toxic. The other syntheses 5,6,9b from the chiral pool materials have been reported for only (2R,8R)-II and involve multiple protection and deprotection steps.

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“…The starting propargyl alcohols 6 and 10 are obtained from asymmetric reduction of the corresponding propargyl ketones with (S)-and (R)-Alpine-Borane (from (-)-and (-t-)-a-pinene), respectively. The isopropyl group imparts essentially complete asymmetric induction, 92% ee for 6 and 10 from 92% ee -pinene.2 Fragment 8 was readily prepared in greater than 98% diasteromeric purity by [2,3]-sigmatropic rearrangement of the in situ generated trimethylsilyl propargyl ether of 7.6 Fragment 12 was prepared by using the Johnson ortho ester Claisen rear-rangement7 of frans-allylic alcohol 11 as the key step. Both (6) (7) Johnson, W. S.; Verthemann, L.; Bartlett, W. R.; Brocksom, T. J.; Li, T.; Faulkner, D. J.; Peterson, M. R. J.…”

mentioning

confidence: 99%