Category:TP3

Revision as of 09:42, 10 August 2010

Triterpene (C30) Classes

環の構造

The basic structure is 4 carbon rings, cyclopenta[a]phenanthrene, gonane, or sterane. The rings B/C are always trans in all natural steroids. If the rings C/D are trans, it is called gonane. If its stereochemistry is unspecified, it is called sterane. Most steroids take gonane form, but in cardenolides and bufanolides, the rings C/D are cis.

Cyclopenta[a]phenanthrene	Gonane

The majority of steroids have methyl groups sticking out from the bridgehead positions C-10 and C-13. When these methyl groups (or hydrogens) stand above the plane, they are called β-configuration. Those below the plane are called α-configuration. If the configuration at any site is unknown, it is indicated as ξ (Greek Xi). By default, hydrogen atoms or substituents at the positions C-8, 9, 10, 13, and 14 are assumed to be 8β, 9α, 10β, 13β, and 14α configurations. C-5 is a special position, because there are as many 5α steroids as 5β are.

cholestane backbone	5α-configuration	5β-configuration

生合成

概要

The starting point is squalene, which is formed by joining two FPPs tail-to-tail. Bacterial cyclases use squalene directly^[1], but those of the other species use 2,3-oxidosqualene for cyclization.

• In bacteria, squalene is cyclized via the 17α-deoxydammarenyl cation to hopene and other triterpenes.
• In eukaryotes, 2,3-oxidosqualene is cyclized via the protosteryl cation to lanosterol (animals and fungi), cycloartenol (plants) or parkeol (sea cucumbers) by a series of 1,2-hydride and methyl shifts (Wagner-Meerwein shifts).^[2]
• In plants, various triterpenes arise from the 17β-dammarenyl cation.

真核生物のオキシドスクアレン環化酵素

Any path of reactions from the root (2,3-oxidosqualene) to any triterpene backbone with a colored background is catalyzed by a single enzyme called oxidosqualene cyclase (OSC) or terpene synthase h (tpsh).^[3]

		2,3-oxidosqualene
lanosterol syntase[4] stepwise cyclization[5]				lupeol synthase stepwise cyclization
17β-protosteryl cation (C-B-C)[6]	1,2-shift	lanosteryl cation (C-C-C)		17β-dammarenyl cation (C-C-C)[7]
D-ring expansion fungus only[8] protostane		1,2-shifts all eukaryotes		D-ring expansion dammarane euphane tirucalane etc.[9]
cation with the chain at C18 or C17 position or		all steroids lanostane cycloartane cucurbitane ergostane etc.	baccharane shionane	baccarenyl cation (C-C-C-C)
E-ring cyclization (from 17β) No 17α known in nature [10]	E-ring cyclization (from 18α)		E-ring cyclization (from 17α/β)	E-ring cyclization (from 18α/β)
arborinyl cation (C-B-C-C)	unnamed cation (C-B-C-C)		21α-hopyl cation (C-C-C-C) 21β-moretyl cation (C-C-C-C)[11]	H18α-lupyl cation (C-C-C-C) H18β-lupyl cation (C-C-C-B)
1,2-shifts E-ring expansion	1,2-shifts E-ring expansion		1,2-shifts E-ring expansion	1,2-shifts E-ring expansion
arborinane (C-B-C-C) stictane (C-B-C-C-C)[12]	hancokinane (C-B-C-C)		hopane (C-C-C-C) gammacerane (C-C-C-C-C) fernane (C-C-C-C) swertane (C-C-C-C-C)	oleanane (C-C-C-C-C) lupane (C-C-C-C) germanicane taraxastane (C-C-C-C-C) ursane (C-C-C-C-C/B) friedomadeirane (C-C-C-C)[13]

1. ↑ Bacterial squalene cyclases can accept oxidosqualene as their substrates, but oxidosqualene usually does not exist in bacteria
2. ↑ In plants, a trace amount of phytosterols comes from lanosterol.
   Ref. Ohyama K, Suzuki M, Kikuchi J, Saito K, Muranaka T (2009) Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis Proc Natl Acad Sci USA 106(3):725-730
   Parkeol is also widespread in plants.
3. ↑ Terpene synthases a-f are responsible for mono-, sesquie- and diterpenes. Tps g is the squalene cyclase.
4. ↑ Lanosterol synthase is the most accessible enzyme among oxidosqualene cyclases, e.g. from mammalian liver or yeast.
   Ref. Corey EJ, Russey WE, Ortiz-de-Montellano PR (1966) 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene J Am Chem Soc 88:4750-1
5. ↑ The cyclization process is stepwise, not concerted as previously thought. As one clue, squalene is not fully folded in the cyclase active site.
   Ref. Reinert DJ, Balliano G, Schulz GE (2004) Conversion of squalene to the pentacarbocyclic hopene. Chem Biol 11:121-6
6. ↑ The C-17 chain of rotosteryl cation is β-configuration, not α.
   Ref. Corey EJ, Virgil SC (1991) An experimental demonstration of the stereochemistry of enzymic cyclization of 2,3-oxidosqualene to the protosterol system, forerunner of lanosterol and cholesterol. J Am Chem Soc 113:4025-6
7. ↑ The C-17 chain of dammarenyl cation is β-configuration.
   Ref. Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configuration transmission in triterpene synthesis. J Org. Chem. 70:5362-75
8. ↑ Oxygenated protostane are known in Cephalosporium caerulens, Fusidium coccineum, and Aspergillus fumigatus (Ascomycota).
   Ref. Hattori H, Igarashi H, Iwasaki S, Okuda S, (1969) Isolation of 3bhydroxy- 4b-methylfusida-17(20)[16,21-cis],24 diene (3b-hydroxyprotosta- 17(20)[16,21-cis],24 diene) and a related triterpene alcohol Tetrahedron Lett 13, 1023–1026
   Tiwari KP, Choudhary RN (1981) Chemical examination of Wisteria sinensis Proc Natl Acad Sci India A 51, 263–271
9. ↑ Dammarane derivatives are unusually prevalent in the genus Euphorbia.
10. ↑ No 17α cyclization for the ring-B boat form. Also no squalene cyclase is known for the ring-B boat form.
    Ref. Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configurational transmission in triterpene synthesis. J Org Chem 70:5362-75
11. ↑ The 21R stereocenter is usually lost in hydride shift.
12. ↑ C-B-C-C-C rings are very rare and stictanediol from Ascomycota Sticta genus is the sole example.
    Ref. Chin WJ, Corbett RE, Heng CK, Wilkins AL (1973) Lichens and fungi. XI. Isolation and structural elucidation of a new group of triterpenes from Sticta coronata, S. colensoi, and S. flavicans. J Chem Soc Perkin Trans 1:1437–46
13. ↑ E-ring cyclization precedes D-ring expansion.

Reviews:

• Xu R, Fazio GC, Matsuda SPT (2004) On the origins of triterpenoid skeletal diversity. Phytochemstry 65:261-291 PMID 14751299

バクテリアのスクアレン環化酵素

Squalene cyclase (SC) or terpene synthase g (tpsg) are found in prokaryotes, ciliates, and lower plants (mosses and ferns) and can convert squalene, which is symmetric, as well as 2,3-oxidosqualene. Main products are hopanol and tetrahymanol, and only generate all-chair cations.

squalene	squalene-hopene cyclase[1]	17α-deoxydammarenyl cation[2]
		D-ring expansion E-ring cyclization from 17α
hopene		hopyl cation

Hopanoids are widespread: they are found in bacteria, ferns, and geological sediments.

1. ↑ SH cyclase is the most investigated enzyme among squalene cyclases.
   Ref. Kannenberg EL, Poralla K (1999) Hopanoid biosyntehsis and function in bacteria. Naturwissenschaften 86:168-76.
2. ↑ The C-17 chain of deoxydammarenyl cation is α-configuration, not β as in eukaryotes.
   Ref. Wendt KU, Schulz GE, Corey EJ, Liu DR (2000) Enzyme mechanisms for polycyclic triterpene formation. Angew Chem, Int Ed 39:2812-33

ID番号の設計

x ... species information

y ... backbone structure (母核構造) 

Symbol at y	Carbons	Steroids	Backbone Structure
GN	C17	gonane
ES	C18	estrane
AD	C19	androstane
PG	C21	pregnane
CA	C24	cholane
CL	C27	cholestane
CM	C28	campestane
EG	C28	ergostane
SG	C29 (4 rings)	stigmastane
PR	C29 (4 rings)	poriferastane

Symbol at y	Carbons	Triterpenoids	Backbone Structure
PS	C30	protostane
EU	C30	euphane
LN	C30	lanostane
CY	C30	cycloartane
FS	C29	fusidane
HP	C30 (5 rings)	hopane
FN	C30 (5 rings)	fernane
CC	C30	cucurbitane
DM	C30	dammarane
BC	C30	baccharane
HL	C30	holostane
PF	C29 (5 rings)	pfaffane
LP	C30 (5 rings)	lupane
OL	C30 (5 rings)	oleanane
FD	C30 (5 rings)	friedelane
TR	C30 (5 rings)	taraxastane
UR	C30 (5 rings)	ursane
SR	C30 (5 rings)	serratane

r ... number of major rings (環構造数) 

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h ... hydroxylation pattern (水酸基数) 

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g ... glycosylation pattern(糖修飾パターン) 

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n ... number of sugars (修飾糖数) 

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c ... serial number (通し番号)