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Revision as of 18:16, 15 December 2010 editChemNerd (talk | contribs)Extended confirmed users17,568 edits removed Category:Oxygen heterocycles; added Category:Benzodioxoles using HotCat← Previous edit		Latest revision as of 00:53, 22 February 2022 edit undoFswitzer4 (talk | contribs)Extended confirmed users10,572 editsm Added/Verified UNII and Verified CAS
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	{{chembox		{{chembox
			| Watchedfields = changed
	| verifiedrevid = 399707582		| verifiedrevid = 402550745
	| ImageFile = Carpanone.png		| ImageFile = Carpanone.png
	| ImageSize =		| ImageSize =
	| IUPACName =		| IUPACName =
	| OtherNames = Cupanone		| OtherNames = Cupanone
	| Section1 = {{Chembox Identifiers		|Section1={{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 21864720		| ChemSpiderID = 21864720
	| InChIKey = WTXORUUTAZJKSN-JMAAQRFFBX		| InChIKey = WTXORUUTAZJKSN-JMAAQRFFBX
Line 13:		Line 14:
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = WTXORUUTAZJKSN-JMAAQRFFSA-N		| StdInChIKey = WTXORUUTAZJKSN-JMAAQRFFSA-N
			| CASNo_Ref = {{cascite|correct|CAS}}
	| CASNo = 26430-30-8		| CASNo = 26430-30-8
⚫	| PubChem = 291296
			| UNII_Ref = {{fdacite|correct|FDA}}
⚫	| SMILES = CC1C=C2C3C(C1C)c4cc5c(cc4OC36C(=CC2=O)OCO6)OCO5
			| UNII = G32K37Q6T4
		⚫	| PubChem = 291296
		⚫	| SMILES = CC1C=C2C3C(C1C)c4cc5c(cc4OC36C(=CC2=O)OCO6)OCO5
	| InChI = 1/C20H18O6/c1-9-3-11-13(21)5-17-20(25-8-24-17)19(11)18(10(9)2)12-4-15-16(23-7-22-15)6-14(12)26-20/h3-6,9-10,18-19H,7-8H2,1-2H3/t9-,10+,18+,19+,20?/m0/s1		| InChI = 1/C20H18O6/c1-9-3-11-13(21)5-17-20(25-8-24-17)19(11)18(10(9)2)12-4-15-16(23-7-22-15)6-14(12)26-20/h3-6,9-10,18-19H,7-8H2,1-2H3/t9-,10+,18+,19+,20?/m0/s1
	}}		}}
	| Section2 = {{Chembox Properties		|Section2={{Chembox Properties
	| C=20|H=18|O=6		| C=20 | H=18 | O=6
	| MolarMass = 354.343 g/mol		| MolarMass = 354.343 g/mol
	| Appearance =		| Appearance =
	| Density =		| Density =
	| MeltingPt =		| MeltingPt =
	| BoilingPt =		| BoilingPt =
	| Solubility =		| Solubility =
	}}		}}
	| Section3 = {{Chembox Hazards		|Section3={{Chembox Hazards
	| MainHazards =		| MainHazards =
	| FlashPt =		| FlashPt =
	| Autoignition =		| AutoignitionPt =
	}}		}}
	}}		}}
			'''Carpanone''' is a naturally occurring ]-type ] most widely known for the remarkably complex way nature prepares it, and the similarly remarkable success that an early chemistry group, that of Orville L. Chapman, had at ] nature's pathway.<ref name=LindsleyRev2011>C.W. Lindsley, C.R. Hopkins & G.A. Sulikowski, 2011, Biomimetic synthesis of lignans, In "Biomimetic Organic Synthesis" (E. Poupon & B. Nay, Eds.), Weinheim: Wiley-VCH, {{ISBN|9783527634767}}, see , accessed 4 June 2014.</ref><ref name=Chapman1971>O.L. Chapman, M.R. Engel, J.P. Springer & J.C. Clardy, 1971, Total synthesis of carpanone, ''J. Am. Chem. Soc.'' '''93''':6697–6698.</ref> Carpanone is an ] first isolated from the ] (''Cinnamomum sp.'') of ] by Brophy and coworkers, trees from which the ] derives its name.<ref name=LindsleyRev2011/><ref name=LironPoli2009>F. Liron, F. Fontana, J.-O. Zirimwabagabo, G. Prestat, J. Rajabi, C. La Rosa & G. Poli, 2009, A New Cross-Coupling-Based Synthesis of Carpanone, Org. Lett., 11(19):4378–4381, DOI: 10.1021/ol9017326, see {{cite web|url=http://202.127.145.151/siocl/siocl_0003/090901hhpdf/090909ol-5.pdf |title=Archived copy |access-date=2014-06-06 |url-status=dead |archive-url=https://web.archive.org/web/20140607003554/http://202.127.145.151/siocl/siocl_0003/090901hhpdf/090909ol-5.pdf |archive-date=2014-06-07 }} or , accessed 4 June 2014</ref> The hexacyclic lignan is one of a class of related ]s isolated from carpano bark as mixtures of equal proportion of the ] of its components (i.e., ]s), and is notable in its stereochemical complexity, because it contains five contiguous stereogenic centers. The route by which this complex structure is achieved through ] involves ] that, almost instantly, take a molecule with little three-dimensionality to the complex final structure. Notably, Brophy and coworkers isolated the simpler ], a ] with a 9-carbon framework, recognized its substructure as being dimerized within the complex carpanone structure,<ref>G.C. Brophy, J. Mohandas, M. Slaytor, T.R. Watson & L.A. Wilson, 1969, Novel lignans from a ''Cinnamomum'' sp. from Bougainville, Tetrahedron Lett. 10:5159-5162.</ref> and proposed a hypothesis of how carpacin was converted to carpanone in plant cells:
	'''Carpanone''' is a naturally occurring ] first isolated from the ] (''Cinnamomum sp.''), from which it derives its name. It is classified as a ].<ref>{{cite journal|doi=10.1071/CH9691803|title=Trans-2-methoxy-4,5-methylenedioxypropenylbenzene (carpacin) from a ''Cinnamomum sp.'' from Bougainville|author=J. Mohandas, M. Slaytor, T.R. Watson|journal=Aust. J. Chem.|year=1969|volume=22|pages=1803–1804}}</ref>
			], and a more common type of ] ] ] whose structure was recognized as being dimerized in carpanone]]
			* carpacin underwent loss of a methyl (-CH<sub>3</sub>) group from the ring methoxy (-OCH<sub>3</sub>) group to provide the phenol, ]carpacin,
			* this ] intermediate then underwent a phenolic coupling to generate a dimeric intermediate, which was
			* followed immediately by a ] (4+2) ] reaction to create 2 new rings, to give the final carpanone product.
			Remarkably, within two years, Chapman and coworkers were able to chemically design a route to ] this proposed biosynthetic route, and achieved the synthesis of carpanone from carpacin in a single "pot", in about 50% yield.<ref name=LindsleyRev2011/><ref name=Chapman1971/>
			Carpanone itself is limited in its pharmacologic and biologic activities, but related analogs arrived at by variations of the Brophy-Chapman approach have shown activities as tool compounds relevant to mammalian exocytosis and vesicular traffic,<ref name=GoessShair2006>Brian C. Goess, Rami N. Hannoush, Lawrence K. Chan, Tomas Kirchhausen, and Matthew D. Shair, 2006, Synthesis of a 10,000-Membered Library of Molecules Resembling Carpanone and Discovery of Vesicular Traffic Inhibitors, ''J. Am. Chem. Soc.'' '''128'''(16): 5391–5403, DOI: 10.1021/ja056338g, see , accessed 4 June 2014.</ref> and provided therapeutic ] in antiinfective, antihypertensive, and hepatoprotective areas.<ref name=LironPoli2009/>
			The original Chapman design and synthesis is considered a classic in total synthesis, and one that highlights the power of biomimetic synthesis.<ref name=LindsleyRev2011/><ref name=NicolaouCTS1>{{cite book |title= Classics in Total Synthesis|last= Nicolaou|first= K. C.|author-link=K. C. Nicolaou |author2=E. J. Sorensen|year= 1996|publisher= VCH|location= Weinheim, Germany|isbn= 978-3-527-29284-4|pages=–97 |url=https://archive.org/details/classicstotalmet00kcni|url-access= limited}}</ref>
	==Total synthesis==		==Total synthesis==
	The first ] of carpanone was published by ] ''et al.'' in 1971. The ] synthesis comprises only two steps beginning with 2-]]; the key step is an ] ] of two identical molecules, which are coupled using a ] ]:		The first ] of carpanone was the ] approach published by Chapman ''et al.'' in 1971. The required desmethylcarpacin (2-]]), shown below as the starting molecule in the scheme, is acquired in two high-yield steps involving three transformations:
			* allylation of the phenolic anion generated after treatment of ] with potassium carbonate and allyl bromide,
	]
			* followed by a thermal ] to move the O-allyl group onto the adjacent site on the aromatic ring, and then
	{{-}}
			* thermal isomerization of the Claisen product, to move the terminal olefin (]) into conjugation with the ring (with e.g., potassium ''tert''-butoxide as base).
	This reaction creates two new rings and forms five contiguous ] centers.<ref name="Nicolaou">{{cite book |title= Classics in Total Synthesis|last= Nicolaou|first= K. C.|authorlink=K. C. Nicolaou |coauthors= E. J. Sorensen|year= 1996|publisher= VCH|location= Weinheim, Germany|isbn= 3-527-29284-5|page= |pages=95–97 |url= |accessdate= }}</ref>
			This procedure is one of several that gives the required ]carpacin (carpacin with the methyl of its methoxy group removed).<ref name=LironPoli2009/> Though oxidative dimerizations of phenols normally used a 1-electron oxidant, Chapman then followed a precedent involving a 2-electron oxidant and treated desmethylcarpacin with PdCl<sub>2</sub> in the presence of sodium acetate (e.g., dissolved in a mixture of methanol and water);<ref name=LindsleyRev2011/><ref name=LironPoli2009/> the reaction was perceived to proceed via a complexation of a pair of carpacins to the Pd(II) metal via their phenolic anions (as shown in scheme, below right),<ref name=NicolaouCTS1/> followed by a classic 8-8' (β-β') oxidative phenolic coupling of the two olefin tails—shown crossing in the image—to give a dimeric ''trans''-''ortho''-]-type of ] intermediate. A particular conformation of this dimer then places a 4-electron ] of one ring over the 2-electron ] of the other (shown adjacent in image for clarity), setting the state for a variant of the ] reaction termed an inverse demand Diels-Alder reaction (see curved arrows in image), which closes the 2 new rings and generates the 5 contiguous ]. The carpanone is produced in yields of ≈50% by the original method, and in yields >90% in modern variants (see below).<ref name=LindsleyRev2011/><ref name=Chapman1971/><ref name=LironPoli2009/> The synthesis of a single diastereomer was confirmed in the original Chapman work, using ].
			] transformation of ]carpacin into carpanone in one pot, via a ] oxidative coupling–Diels Alder reaction sequence.<ref name=NicolaouCTS1/> Note, in the second image in the scheme, the two lines crossing at the top are the two molecules overlapping each other (and do not imply chemical bonds). In this scheme, Pd (II) is shown forming a complex between two ''monomers'' of carpacin, then mediating oxidative 8-8' (β-β') phenolic coupling of their alkene tails to generate a ''dimer'', a ''trans''-''ortho''-] intermediate, followed immediately by an ''endo''-selective inverse electron-demand hetero-] reaction (see ]),<ref name=LindsleyRev2011/> to close the rings and generates the ].]]
⚫	==References==
			For the elegance of its "one-pot construction of a tetracyclic scaffold with complete stereocontrol of five contiguous stereo centers",<ref name=LindsleyRev2011/> the original Chapman design and synthesis is "ow considered a classic in total synthesis" that "highlights the power of biomimetic synthesis".<ref name=LindsleyRev2011/><ref name=NicolaouCTS1/>
			== Extensions of the system ==
			The Chapman approach has been applied in a variety of ways since its original report, varying substrates, oxidants,<ref>Per Lindsley et al., see following, oxidant systems, generally including dioxygen, adventitious or otherwise, include azobisisobutyronitrile, Ag<sub>2</sub>O, M(II) salen systems (M=Co, Mn, Fe), singlet oxygen (hν, Rose Bengal), dibenzoyl peroxide, and IPh(OAC)<sub>2</sub>.</ref> and other aspects (and so synthesis of carpanone has subsequently been achieved by "quite a few research groups");<ref name=LindsleyRev2011/><ref name=LironPoli2009/> the actual mechanism of Pd(II) action is likely more complex than the original conjecture, and there is evidence that the mechanism, broadly speaking, depends on actual conditions (specific substrate, oxidant, etc.).<ref name=LironPoli2009/> Various groups, including the laboratories of Steve Ley, Craig Lindley, and Matthew Shair, have succeeded in extending the Chapman method to ''solid-supported synthesis'', i.e., phenolic starting materials on polymeric supports, thus allowing the generation of libraries of carpanone analogs.<ref name=LindsleyRev2011/><ref name=GoessShair2006/> A hetero-8-8' oxidative coupling system akin to the Chapman approach has been developed that uses IPh(OAC)<sub>2</sub>, and that allows for preparation of more electron rich homodimers, and for hetero-tetracyclic analogs of carpanone.<ref>C.W. Lindsley, L.K. Chan, B.C. Goess, R. Joseph & M.D. Shair, 2001, Solid-phase biomimetic synthesis of carpanone-like molecules, J. Am. Chem. Soc. '''122''', 422–423.</ref>
		⚫	==References and notes==
	{{reflist}}		{{reflist}}
			== Further reading ==
			* Baxendale, I. R.; Lee, A.-L.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 2002, 1850–1857.
			* Goess, B. C.; Hannoush, R. N.; Chan, L. K.; Kirchhausen, T.; Shair, M. D. J. Am. Chem. Soc. 2006, 128, 5391–5403.
			* Daniels, R. N.; Fadeyi, O. O.; Lindsley, C. W. Org. Lett. 2008, 10, 4097–4100.
	]		]
	]		]
	]		]
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