Jiadifenolide

Jiadifenolide
Names
	IUPAC name (1R,2R,6R,7R,9S,10R,11R)-6,9-Dihydroxy-2,11-dimethyl-4,8,14-trioxapentacyclo[7.4.2.17,10.01,10.02,6]hexadecane-5,15-dione
Identifiers
CAS Number	1193637-57-8 ;
3D model (JSmol)	Interactive image;
ChemSpider	28287016;
PubChem CID	44542225;
	InChI InChI=1S/C15H18O7/c1-7-3-4-13-11(2)6-20-9(16)14(11,18)8-5-12(7,13)15(19,21-8)10(17)22-13/h7-8,18-19H,3-6H2,1-2H3/t7-,8-,11+,12-,13-,14-,15-/m1/s1 Key: YUHGKFNPDNMLHL-VNSIYCHCSA-N;
	SMILES O=C1OC[C@@]2(C)[C@@]3(OC4=O)[C@@]([C@H](C)CC3)([C@]4(O)O5)C[C@]5([H])[C@]21O;
Properties
Chemical formula	C15H18O7
Molar mass	310.302 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Jiadifenolide is a sesquiterpenoid natural product with neurotrophic activity, found in Illicium jiadifengpi. Its biological activity and congested polycyclic structure have made it a popular target for total synthesis.

Isolation and bioactivity

The seco-prezizaane-type sesquiterpenoid jiadifenolide was isolated in 2009 from the fruit of the flowering plant Illicium jiadifengpi.^[1] Chemical synthesis enabled preliminary assessment of its in vitro activity in promoting neurite outgrowth.^[2]

Chemical synthesis

Jiadifenolide has been the subject of synthetic study in several academic labs.^[3]^[4]

The first total synthesis, reported in 2009, employed an asymmetric Robinson annulation and a translactonization reaction to construct the core of the molecule.^[5] Two further syntheses, a chiral-pool approach from (+)-pulegone^[6] and a racemic synthesis relying on a samarium diiodide–mediated reductive cyclization,^[7] were reported almost simultaneously in 2014. A second chiral-pool synthesis (from (+)-citronellal) reported in 2015 shortened the synthetic sequence, with a double Michael addition as the key transformation of eight steps, allowing the synthesis of gram-scale quantities of jiadifenolide.^[8]

References

^ Kubo, Miwa; Okada, Chihiro; Huang, Jian-Mei; Harada, Kenichi; Hioki, Hideaki; Fukuyama, Yoshiyasu (19 November 2009). "Novel Pentacyclic seco-Prezizaane-Type Sesquiterpenoids with Neurotrophic Properties from Illicium jiadifengpi". Organic Letters. 11 (22): 5190–5193. doi:10.1021/ol9021029. PMID 19873982.
^ Trzoss, Lynnie; Xu, Jing; Lacoske, Michelle H.; Mobley, William C.; Theodorakis, Emmanuel A. (10 May 2013). "Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies". Chemistry: A European Journal. 19 (20): 6398–6408. doi:10.1002/chem.201300198. PMC 3875175. PMID 23526661.
^ Downer-Riley, Nadale K.; Jackson, Yvette A. (2012). "Highlight syntheses". Annual Reports on the Progress of Chemistry, Section B. 108: 147. doi:10.1039/c2oc90006h.
^ "(−)-Jiadifenolide". Chemistry World. Royal Society of Chemistry. Retrieved 29 July 2015.
^ Xu, Jing; Trzoss, Lynnie; Chang, Weng K.; Theodorakis, Emmanuel A. (11 April 2011). "Enantioselective Total Synthesis of (−)-Jiadifenolide". Angewandte Chemie International Edition. 50 (16): 3672–3676. doi:10.1002/anie.201100313. PMC 3159889. PMID 21400650.
^ Siler, David A.; Mighion, Jeffrey D.; Sorensen, Erik J. (19 May 2014). "An Enantiospecific Synthesis of Jiadifenolide". Angewandte Chemie International Edition. 53 (21): 5332–5335. doi:10.1002/anie.201402335. PMC 4153357. PMID 24757120.
^ Paterson, Ian; Xuan, Mengyang; Dalby, Stephen M. (7 July 2014). "Total Synthesis of Jiadifenolide". Angewandte Chemie International Edition. 53 (28): 7286–7289. doi:10.1002/anie.201404224. PMC 4320761. PMID 24861364.
^ Lu, Hai-Hua; Martinez, Michael D.; Shenvi, Ryan A. (15 June 2015). "An eight-step gram-scale synthesis of (−)-jiadifenolide". Nature Chemistry. 7 (7): 604–607. Bibcode:2015NatCh...7..604L. doi:10.1038/nchem.2283. PMID 26100810. S2CID 10715433.

[Kubo-1] Kubo, Miwa; Okada, Chihiro; Huang, Jian-Mei; Harada, Kenichi; Hioki, Hideaki; Fukuyama, Yoshiyasu (19 November 2009). "Novel Pentacyclic seco-Prezizaane-Type Sesquiterpenoids with Neurotrophic Properties from Illicium jiadifengpi". Organic Letters. 11 (22): 5190–5193. doi:10.1021/ol9021029. PMID 19873982.

[Theodorakis1-2] Trzoss, Lynnie; Xu, Jing; Lacoske, Michelle H.; Mobley, William C.; Theodorakis, Emmanuel A. (10 May 2013). "Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies". Chemistry: A European Journal. 19 (20): 6398–6408. doi:10.1002/chem.201300198. PMC 3875175. PMID 23526661.

[Downer-Riley-3] Downer-Riley, Nadale K.; Jackson, Yvette A. (2012). "Highlight syntheses". Annual Reports on the Progress of Chemistry, Section B. 108: 147. doi:10.1039/c2oc90006h.

[BRSM-4] "(−)-Jiadifenolide". Chemistry World. Royal Society of Chemistry. Retrieved 29 July 2015.

[Theodorakis2-5] Xu, Jing; Trzoss, Lynnie; Chang, Weng K.; Theodorakis, Emmanuel A. (11 April 2011). "Enantioselective Total Synthesis of (−)-Jiadifenolide". Angewandte Chemie International Edition. 50 (16): 3672–3676. doi:10.1002/anie.201100313. PMC 3159889. PMID 21400650.

[Sorensen-6] Siler, David A.; Mighion, Jeffrey D.; Sorensen, Erik J. (19 May 2014). "An Enantiospecific Synthesis of Jiadifenolide". Angewandte Chemie International Edition. 53 (21): 5332–5335. doi:10.1002/anie.201402335. PMC 4153357. PMID 24757120.

[Dalby-7] Paterson, Ian; Xuan, Mengyang; Dalby, Stephen M. (7 July 2014). "Total Synthesis of Jiadifenolide". Angewandte Chemie International Edition. 53 (28): 7286–7289. doi:10.1002/anie.201404224. PMC 4320761. PMID 24861364.

[Shenvi-8] Lu, Hai-Hua; Martinez, Michael D.; Shenvi, Ryan A. (15 June 2015). "An eight-step gram-scale synthesis of (−)-jiadifenolide". Nature Chemistry. 7 (7): 604–607. Bibcode:2015NatCh...7..604L. doi:10.1038/nchem.2283. PMID 26100810. S2CID 10715433.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]