Santonin. III.<sup>1</sup> The Total Synthesis of Santonin<sup>2</sup>

Abe, Yasuo; Harukawa, Tadatsugu; Ishikawa, Hisashi; Miki, Takuichi; Sumi, Masao; Toga, Tadashi

doi:10.1021/ja01588a043

Cited by 34 publications

(10 citation statements)

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“…384 K) suitable for X-ray diffraction analysis were obtained from ether±hexane. The stereochemistry found agrees with that previously assigned to the isomer (of negative optical rotation) having this melting point (Miki, 1955;Abe et al, 1956;Djerassi et al, 1958;Ando et al, 1980). The asymmetric unit of (I), with the atom numbering shown only for molecules (IA); the unlabeled molecule is (IB).…”

Section: Methodssupporting

confidence: 87%

(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

Thompson

Lalancette

2003

Acta Crystallogr C

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In the title compound, C(15)H(24)O(3), derived from a naturally occurring sesquiterpenoid, the asymmetric unit consists of two molecules differing by 167.4 (8) degrees in the rotational conformation of the carboxyl group. Each molecule aggregates separately with its own type as carboxyl-to-ketone hydrogen-bonding catemers [O...O = 2.715 (6) and 2.772 (6) A, and O-H...O = 169 and 168 degrees ]. This generates two crystallographically independent single-strand hydrogen-bonding helices passing through the cell in the b direction, with opposite end-to-end orientations. One intermolecular C-H...O=C close contact exists for the carboxyl group of one of the molecules. The structure is isostructural with that of a closely related unsaturated keto acid reported previously.

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Section: Methodssupporting

confidence: 87%

(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

Thompson

Lalancette

2003

Acta Crystallogr C

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“…Dimethyl Bicyclo[2.2.2]octane-l,2-dicarboxylate (8).-To 5 ml. of absolute methanol was added 0.25 g. of platinum oxide.…”

Section: Methodsmentioning

confidence: 99%

“…distinction between the exo and the endo isomers arises from the magnetic shielding effect of the 5,6-double bond at the region of C-2 that is endo to the double bond. 8 The methyl peak of the C-2 carbomethoxy group may be expected to appear at higher field in 19 than in 7 and the C-2 hydrogen may be expected to appear at higher field in 7 than in 19. Such differences are seen in the n.m.r.…”

mentioning

confidence: 99%

Bicyclo[2.2.2]octane-1,2-dicarboxylic Acid¹

Kazan¹,

Greene²

1963

J. Org. Chem.

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Bicyclo [2.2.2 ]octane-1,2-dicarboxylic Acid 2965 through which nitrogen was passed. The flask containing the solution, covered by an atmosphere of nitrogen, was tightly stoppered and allowed to stand at room temperature for 2 days.The brown liquid was then distilled under nitrogen giving a clear liquid (4.35 g., 0.022 mole, 38%), b.p. 54°(1 mm.). The distillate showed only ester absorption in the infrared.

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“…The mixture was heated to reflux 2O-Methyl-2-( la-hydroxy-4a@,8-dimethyl-l,2,3,4,4a,8a@-hexahydronaphth-2@-yl)acetic A c i d L a c t o n e (15). To a solution of 0.069 mL (0.45 nimol) of diisopropylamine in 3 mL of tetrahydrofuran a t -78 "C was added a solution of 0.18 mL (0.40 mmol) of 2.29 M nbutyllithium in hexane and 0.05 mL of HMPA.…”

Section: L-(4-ethylthio-4-ethylsulfinylbutyl)-l3-dimethylcyclo-mentioning

confidence: 99%

Stereocontrolled total synthesis of .alpha.- and .beta.-santonin

Marshall¹,

Wuts²

1978

J. Org. Chem.

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A ttstal synthesis of racemic cy-and p-santonin is described. The synthetic sequence invo)ves reduction-alkylation of m-toluic acid with lithium in ammonia followed by methyl iodide. Homologation of the resulting l-methyl-1,4-dihydro-m-toluic acid was effected by reduction using lithium aluminum hydride, oxidation with N-chlorosuccinimide-dimethyl sulfide reagent, and condensation of the resulting aldehyde with triethyl phosphonoacetate to give the acrylic ester derivative. Reduction with lithium in ammonia-ethanol yielded the propanol-substituted 1,4-dihydro-m-xylene, which was transformed to the bromide and alkylated with the lithium salt of the monosulfoxide of formaldehyde diethyl thioacetal. Treatment with acid effected cyclization via the butanal, affording 4a,8dimethyl-1,2,3,4,4a,8a-hexahydronaphthalen-1-01 (9). Oxidation to the ketone and alkylation using ethyl iodoacetate gave the expected keto ester 11, which was reduced to a mixture of diols. These were separated and the trans isomer was oxidized to the trans lactone 14 using silver carbonate on Celite. Alkylation with methyl iodide yielded the 6 methyl isomer 15, which could be epimerized to the more stable cy isomer 16. Photooxygenation of each of these isomers afforded a-santonin (17) and a-santonin (18), along with the corresponding endoperoxides 19 and 20.6 with lithium in ammonia-ethanol. The derived bromide 7 afforded the thioacetal monosulfoxide 8 upon treatment with the lithio derivative of ethyl thioethoxymethyl ~ulfoxide.~ Treatment of this sulfoxide derivative with perchloric acid led directly to alcohol 9, presumably via the derived butyraldehyde. The entire sequence to this point can be effected in 40% overall yield.5Oxidation of alcohol 9 using dimethyl sulfide-N-chlorosuccinimide gave ketone 10. This ketone, upon treatment with lithium diisopropylamide and ethyl iodoacetate, yielded the expected kinetic alkylation product, keto ester 11.Our expectation of this reaction outcome was based on steric and stereoelectronic considerations. Accordingly, the concave geometry of dienone 10 and any intrinsic preference for axial alkylation should favor attack on the enolate 10a from the convex (top) face as shown below.6 We were not particularly concerned about formation of the bridgehead enolate 10b and/or isomerization of ketone 10 for two reasons. In the first place, the ring fusion cu-hydrogen of dienone 10 cannot assume a favorable perpendicular orientation toJhe P,y double bond and the ketone carbonyl simultaneously (see 1Oc 5 loa).

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Santonin. III.¹ The Total Synthesis of Santonin²

Cited by 34 publications

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(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

Bicyclo[2.2.2]octane-1,2-dicarboxylic Acid¹

Stereocontrolled total synthesis of .alpha.- and .beta.-santonin

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Santonin. III.1 The Total Synthesis of Santonin2

Cited by 34 publications

References 0 publications

(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

(–)-2-(1,2,3,4,4a,5,6,7,8,8aα-Decahydro-4aβ,8α-dimethyl-7-oxo-2β-naphthyl)propionic acid: catemeric hydrogen bonding in a bicyclic sesquiterpenoid ζ-keto acid

Bicyclo[2.2.2]octane-1,2-dicarboxylic Acid1

Stereocontrolled total synthesis of .alpha.- and .beta.-santonin

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Santonin. III.¹ The Total Synthesis of Santonin²

Bicyclo[2.2.2]octane-1,2-dicarboxylic Acid¹