Cembranoids of Marine Invertebrates! Hundreds of Natural Products, So Little Time H 3 CO 2 C OH OH mandapamate H H O CO 2 CH 3 H 3 CO O O O HO H 3 CO O O OH havellockate 1 3 4 6 8 O O O O CH 3 O 2 C Sinularia granosa 4 3 1 Jennifer Roizen Stoltz Group Literature Presentation Noyes 147 8pm, April 17, 2006 O O O O H 1 4 8 12 intricarene 6 O O HO H AcO O O H O H H 3 CO 2 C H providencin Pseudopterogorgia kallos O O rubifolide Gersemia rubiformis O juncin N Junceella juncea O O OAc AcO H 38 HO HO 2 C OAc OAc Cl O 1 8 9 3 11 4 Pachyclavulariolide O Pachyclavularia violacea O O O H HO H O O OH sinulariolone Sinularia flexibilis 1 4 11 8 O HO O 5 11 4 1 4 1
48
Embed
Cembranoids of Marine Invertebrates!Cembranoids of Marine Invertebrates! Hundreds of Natural Products, So Little Time H3CO2C OH OH mandapamate H H O CO2CH3 H3CO O O HO O H3CO O O OH
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Cembranoids of Marine Invertebrates!Hundreds of Natural Products, So Little Time
H3CO2C OH
OH
mandapamate
HH
O
CO2CH3H3CO
O
O
OHO
H3COO
O
OH
havellockate
1
3
4
6
8
O
O
O
OCH3O2C
Sinularia granosa
43
1
Jennifer RoizenStoltz Group Literature Presentation
Skeletal Origincembranoids are found in marine invertebrates, insects and tobacco
A AA
A A
found in insects:
found in tobacco: 1
4
8
11
3
81
11
4
coralloidolide FAlcyonium coralloides
2,6-cyclized cembranoid
sarcophytol LSarcophyton glaucum
absolute stereochemistry
capnosane(found in tobacco and marine)
3 811
4
1
Coralloidoilide F: D'Ambrosio, M.A. et al. Helv. Chim. Acta, 1990, 73, 804-807; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Cembrene: Zhang, T. et al. Synthesis 2001, 3, 393; sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816.
Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196; Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Erythrolide V: Andersen, R. J. et al. Eur. J. Org. Chem. 2003, 3515.Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 ; isolation: Rodríguez, A. D. Chem. Pharm. Bull. 1995, 43, 1853.
Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate: Higa, T. J. Nat. Prod. 2004, 67, 1368.Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
Skeletal Termsexamples
A AA
AA
sclerophytin Atotal syntheses
cladiellin
O
3
8
111
4
OH
H
HOH
OH
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
asbestinin
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
Aglantha digitale: Fautin, Daphne G. and Romano, Sandra L. 1997. Cnidaria. Sea anemones, corals, jellyfish, sea pens, hydra. Version 24 April 1997. http://tolweb.org/Cnidaria/2461/1997.04.24 in The Tree of Life Web Project, http://tolweb.org
Taxonomic relationships: Coll, John C. Chem. Rev. 1992, 92(4), 613-631.Cool taxonomic tree: http://www.aims.gov.au/pages/reflib/bigbank/images/bb44a.gif
Aglantha digitalemouth, radial symmetry, gonads,
nematocysts (tentacles with singing cells), carnivorous
PHYLUMCoelenterata
(Cnidaria)
SUBPHYLUMAnthozoa
(lack medusa stage= "adult" sexual phase)
(other SUBPHYLUMMedusozoa)
CLASSAlcyontaria
(8 pinnate tentacles / polyp)
Zoantharia(6 pinnate tentacles / polyp)
ORDERAlcyonacea
Gorgonacea
Pennatulacea
Stolonifera
Telestacea
Coenothecalea
Scleractina
Actiniaria
Corallimorpharia
Zoanthiniaria(Zoanthidae)
soft corals0-75% CaCO3
per colony
hard corals95% CaCO3per colony
Alcyonium variable
Acropora(scleractina)
Taxonomic Relationships
Lobophytum compactum: http://www.reefed.edu.au/explorer/landscapes/reefs/Pseudopterolide: Fenical, W.; Clardy, J. et al. J. Am. Chem. Soc. 1982, 104, 6463-6466.
Isolobophytolide: Michalek-Wagner, K. et al. Marine Biology 2001, 138, 753-760.Kallolide A: Kerr, R. G. et al. Mar. Ecol. Prog. Ser. 2005, 303, 105-111.
Coralssimple animals with endo-symbiotic algae (zooxanthellae)
MEP in plastids(monoterpenes, diterpenes, sesquiterpenes, tetraterpenes)
MVA
OPP
Dewick, P. M. Nat. Prod. Rep. 2002, 19, 181-222 (review).Eisenreich, W. et al. Cell. Mol. Life Sci. 2004, 61, 1401-1426 (review).
chain length control: Nishino, T. et al. J. Biol. Chem. 1996, 27(31), 18831-18837.residues binding GPP and IPP: Koyama, T. et al. Biochemistry 1996, 35(29), 9533-9538.
Casbene examples (in review): Dewick, P. M. Nat. Prod. Rep. 1999, 16, 97-130.
Away We GoTo a Cembrane via Geranylgeranyl Diphosphate
OPP(IPP)
OPPOPP(DMAPP) (IPP)
+geranyl diphosphate
synthaseOPP
geranyl diphosphate (GPP)
+farnesyl diphosphate
synthase
catalysis viaMg2+-bound to aspartates (2)
binding vialysines (2) and aspartate (1)
OPP(IPP)farnesyl diphosphate (FPP)
geranylgeranyl
diphosphate synthase+OPP
geranylgeranyl diphosphate (GGPP)
cembrane
SN1
metal-initiated(casbene synthase)
geranylgeranyl diphosphate
PPO H
:Bcasbene
(a cembranoid)
Biosynthesis of Cembranoids v. Non-cembranoidsrevisiting skeletal terms
A AA
A A
cembrane
1
84
dolabellyl cation
verticillyl cationgeranylgeranyl diphosphate
PPO
1
84
geranylgeranyl diphosphate
OPP
1
84
vibsyl cation
1
84
dolabellane scaffold
SN1
metal-initiatedenzymatic
Dolabellane review: Hiersemann, M.; Helmboldt, H. Top. Curr. Chem. 2005, 243, 73-136.Verticilene and Casbene examples: Dewick, P. M. Nat. Prod. Rep. 1999, 16, 97-130 (review).
(1S)-verticilene
SN1
metal-initiated(casbene synthase)
geranylgeranyl diphosphate
PPO
SN1
metal-initiatedenzymatic
H
:Bcasbene
(a cembranoid)
HH
H
sarcophytol LSarcophyton glaucum
absolute stereochemistry
38
11
4
1
Aquariolide A: Andersen, R. J. Org. Lett. 2002, 4, 4085; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816;Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196.
Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate:
Higa, T. J. Nat. Prod. 2004, 67, 1368; Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
More Complex CembranoidsA AA
AA
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
Ineleganolide: Duh, C.-Y. et al. Tetrahedron Lett. 1999, 40, 6033-6035.Mandapamates, havellockate norcembrene and biosynthetic proposal thereof: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.
Sinulochmodin C and sinuleptolide: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.Disclaimer: Retrosynthetic analysis for ineleganolide, sinuleptolide proposed by me.
Biosynthetic proposal: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.
Proposed Biogenesis of Havellockate
H3CO2C OH
OH
HO
CO2CH3O
O
O
O
OCH3O2C
R
Sinularia granosa, R=Hhypothetical, R=CO2CH3
O
O
OHO
H3COO
O
OH
havellockate
1
3
4
6
8
8
34
43
1
O
OHO
H3COO
OH
1
3
4
6
8
H3CO2CHO
rearrangementhydrolysis
lactonization
H3CO2C OH
OHR1H
O CO2R3
O4
3
1
6
bond cleavagelactonization
H
Diels-Alderepoxidation
furan opening
H3CO2C O
OHO
CO2CH3O
8
34
enolizationrearrangement
5
11
Ineleganolide: Duh, C.-Y. et al. Tetrahedron Lett. 1999, 40, 6033-6035.Mandapamates, havellockate norcembrene and biosynthetic proposal thereof: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.
Sinulochmodin C and sinuleptolide: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.Disclaimer: Retrosynthetic analysis for ineleganolide, sinuleptolide proposed by me.
Mandapamates, havellockate norcembrene and biosynthetic proposal thereof: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.Plumarellide and plumarellic acid: Stonik, V. A. Tetrahedron Lett. 2002, 43, 315-317.
C(1)–C(8) StereochemistryNot Enough Data
H3CO2C OH
OH
mandapamate
HH
O
CO2CH3
H3CO2C OH
OH
isomandapamateR1=b-H, R2=CH3, R3=CH3
bishomoisomandapamateR1=a-H, R2=Et, R3=Et
R1H
O
R2O CO2R3H3CO
O
O
OHO
H3COO
O
OH
havellockatex-ray
1
3
4
6
8
OH
plumarellideNOE with CH3-19 and H-5,7,9β
HH
O
CH2OHHO
OO
H OH
plumarellic acidNOE with CH3-19 and H-5,7,9α,β
HH
O
CH2OHHO
OH
H
EtO2C
O
O
O
OCH3O2C
R
Sinularia granosa, R=Hx-ray
hypothetical, R=CO2CH3
43
188
97
5 5
11
Ineleganolide: Duh, C.-Y. et al. Tetrahedron Lett. 1999, 40, 6033-6035.Mandapamates, havellockate norcembrene and biosynthetic proposal thereof: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.
Sinulochmodin C and sinuleptolide: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.Disclaimer: Retrosynthetic analysis for ineleganolide, sinuleptolide proposed by me.
Ineleganolide: Duh, C.-Y. et al. Tetrahedron Lett. 1999, 40, 6033-6035.Sinulochmodin C, sinuleptolide and scabrolides: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.
Rameswaralide: Ramesh, P. Tetrahedron Lett. 1998, 38, 8271-8220.Dissectolide: Iguchi, K. J. Org. Chem. 1996, 61, 5998-6000.Horolide: Radhika, P. et al. J. Nat. Prod. 2002, 65, 737-739.
The depicted yonaronlide: Iguchi, K. Tetrahedron Lett. 1995, 36, 8807-8808.Disclaimer: Biosynthetic relationships of all but sinulochmodin C postulated by me.
O
O
O
O
O
sinulochmodin CSinularia lochmodes
H
H4
8
O
OHH
OH
O
OH
O
H
dissectolide
O
O
O
O
scabrolide B
HOH
horiolide
10OO
O OH
1
8
4
13 O
H H
H
O
O
O
O
(yonaronlide)
C(1)–C(8) Stereochemistryof Compounds Derived from Sinuleptolide-Like Intermediates
O
O
O
OCH3O2C
R
Sinularia granosa, R=Hhypothetical, R=CO2CH3
43
1
OO
O O
O
H
H
ineleganolideSinularia inelegans
O
O
O
O OHH
O
sinuleptolideabsolute stereochemistry (Mosher)
H
1R4 8
rameswaralide
OO
OOH
CO2CH3
OH
10
8
O
O
O
O
HOH
scabrolide A
5
11 11
Absolute Stereochemistry of SinuleptolideForays into Mosher's Ester Analysis
O
O
O
O OR H
O
H5
1R
+0.05
+0.09+0.02+0.03
+0.01
+0.02
-0.11-0.01-0.03
-0.01
-0.01
1H-NMR shifts (ppm):∆δ= δs-δR
magnetic anisotropy(ring current drawn)
externalmagneticfield
SHIELDINGregion
(above and below ring)
DESHIELDINGregion
(in plane of ring)
Explanation of magnetic anisotropy: Ege, Seyhan Organic Chemistry: Structure and Reactivity (1994 3rd edition, USA), p. 409.Mosher's method: Kakisawa, H. et al. J. Am. Chem. Soc. 1991, 113(11), 4092-4096.
Sinuleptolide: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.
O
H OCF3
Ph OCH3L1
L2 O
H OCF3
H3CO PhL1
L2
(S)-MTPA ester (R)-MTPA ester
shieldedshielded
so for L1, ∆δ= δs-δR > 0and for L2, ∆δ= δs-δR < 0
L1 L2
Ineleganolide: Duh, C.-Y. et al. Tetrahedron Lett. 1999, 40, 6033-6035.Mandapamates, havellockate norcembrene and biosynthetic proposal thereof: Anjaneyulu, A. S. R. et al. Indian Journal of Chemistry 2000, 39B, 530-535.
Sinulochmodin C and sinuleptolide: Sheu, J.-H. et al. Org. Lett. 2005, 7(17), 3813-3816.Disclaimer: Retrosynthetic analysis for ineleganolide, sinuleptolide proposed by me.
Aquariolide A: Andersen, R. J. Org. Lett. 2002, 4, 4085; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816;Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196.
Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate:
Higa, T. J. Nat. Prod. 2004, 67, 1368; Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
More Complex CembranoidsA AA
AA
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
Bipinnatin J–kallolide A cycloisomerization: Rodríguez, A. D. et al. J. Org. Chem. 1998, 63(3), 420-421.Bipinnatin J–pinnatin C cycloisomerization: Rodriguez, A. D. et al. J. Org. Chem. 1998, 63(13), 4425-4432.
Hypothesized biosynthetic relationship between intricarene, BSK, rubifolide and bipinnatin J: Trauner, D. et al. Org. Lett. 2006, 8(2), 345-347.Enantioselective total synthesis of rubifolide: Marshall, J. A. et al. J. Org. Chem. 1997, 62(13),4313-4320.
Rubifolide isolation: Williams, D. et al. J. Org. Chem. 1987, 52, 332.Verrillin isolation: Cichewicz, R. H. J. Am. Chem. Soc. 2004, 126, 14910; Williams, D. E. J. Nat. Prod. 2004, 67, 2127.
Gersolanoids, Pseudopteranes, and more!
O
OO
OH
HO
H
H HOOH
H
AcO
1
4
bielschowskysinPseudopterogorgia kallos
O
O
bipinnatin Jabsolute stereochemistryby synthesis of kallolide A
O
HO
[2+2] oxidation
O
O
O
O
H1
4 8
12
intricarene
formaloxidative
[5+2]
12
6
6
O
O
O
HO
kallolide Aabsolute stereochemistry
hν, 2 hCH3CN, 25 °C, 40%1,3-allylic shift
10
7
7
10
O
H
O
HO
pinnatin Cabsolute stereochemistry
by synthesis from bipinnatin J
OO
hν (minor)1,2-migration(antarafacial)
O
O
rubifolideenantioselective total syntheses
Gersemia rubiformis
O
O
O
HO H
AcOO
O
H
O
H
H3CO2C
H
providencinPseudopterogorgia kallos
O
O O
O
O
O H
HO
H
H OH
1
4
verrillinPseudopterogorgia bipinnata
[3+2]1 8 1 8
1
4
1
48
Enantioselective total synthesis of unnatural rubifolide: Marshall, J. A. et al. J. Org. Chem. 1997, 62(13),4313-4320.
Enantioselective Total Synthesis of unnatural Rubifolide O
O
O
HO
8 steps TBSO
O
O
O
OCO2CH3
MOMO
O
OPMBMOMO
OTBS
•
SnBu3
O
OR
•
O
OR
OMOM
5 steps
(66% yield)+
8 diastereomers
1. BF3•OEt22. Dess-Martin, NEt3
(74% yield)
1. AgNO3, silica gel2. p-TsOH
(61% yield)
R=H, 2 diastereomers, undisplayedconverted to desired over 2 steps
in 96% yieldR=COCF3 (reaction intermediate)
R=CO2CH3
R=H
3
8
11
8
11
1
8
11
13
55
81
3
1
3
81
K2CO3, MeOH(96% yield)
Pd(PPh3)4, CO, THF2,6-lutidine, Tf2O
then H2O(49% yield)
Enantioselective total synthesis of kallolide A: Marshall, J. A. et al. J. Org. Chem. 1998, 63(17), 5962-5970.
Enantioselective Total Synthesis of Kallolide A
8
O
O
O
HO 7
10
O7
O
SEMOO
R2
R3
R1
O
EtO2C
O
Bu3Sn ODPS
CO2HCO2H
2,6-(OMe)2C6H3CO2
OHBH3•THF (1 eq), EtCN, Tf2O (2 eq)
(24% yield, 90% ee)2
2
2
R1=OH, R2=ODPS, R3=CO2EtR1=OSEM, R2=Cl, R3=OH
7
111
11
3-steps
NaH, Bu4NI
PhCH3(66% yield)
8
O
OH
SEMO 7
102
BuLi
THF–pentane(73% yield)
Pd2dba3, Ph3P, COTMSCH2CH2OH
THF(73% yield)
8
OSEMO 7
102
•
CO2CH2CH2TMS
4 steps
Bipinnatin J–kallolide A cycloisomerization: Rodríguez, A. D. et al. J. Org. Chem. 1998, 63(3), 420-421.Bipinnatin J–pinnatins cycloisomerization: Rodriguez, A. D. et al. J. Org. Chem. 1998, 63(13), 4425-4432.Enantioselective total synthesis of kallolide A: Marshall, J. A. et al. J. Org. Chem. 1998, 63(17), 5962-5970.Enantioselective total synthesis of rubifolide: Marshall, J. A. et al. J. Org. Chem. 1997, 62(13),4313-4320.Synthesis of deoxypukalide from pukalide and other: Marshall, J. A. J. Org. Chem. 2001, 66, 8037-8041.
Absolute Stereochemistries of 3-Furanocembranoids
1 8O
O
bipinnatin Jabsolute stereochemistryby synthesis of kallolide A
O
HO
12
6
O
O
O
HO
kallolide Aabsolute stereochemistry
hν, 2 hCH3CN, 25 °C, 40%1,3-allylic shift
8
10
7
7
10
O
H
O
HO
pinnatin Cabsolute stereochemistry
by synthesis from bipinnatin J
OO
hν (minor)1,2-migration(antarafacial)
1 8O
O
rubifolideenantioselective total syntheses
Gersemia rubiformis
O
O
O
H
O
pinnatin Aabsolute stereochemistry
by synthesis from kallolide A
+
O
OO
O
pukalideSinularia polydactyla
absolute configuration by synthesis of unnatural enantiomer of deoxypukalide
H3CO2C
sarcophytol LSarcophyton glaucum
absolute stereochemistry
38
11
4
1
Aquariolide A: Andersen, R. J. Org. Lett. 2002, 4, 4085; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816;Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196.
Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate:
Higa, T. J. Nat. Prod. 2004, 67, 1368; Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
More Complex CembranoidsA AA
AA
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
Hypothetical biosynthetic pathway extrapolated from: Wahlberg, I.; Eklund, A.-M. Prog. Chem. Org. Nat. Prod. 1992, 60, 1-141.Sclerophytins: Paquette, L. A. J. Nat. Prod. 2002, 65, 126; Paquette, L. A. The Chemical Record, 2001, 1, 311.
Alcyonin misassigned: Kakisawa, H. Chem. Lett. 1988, 1077; reassigned: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650.Polyanthellin A: Rodríguez, A. D. J. Nat. Prod. 2003, 66, 357; enantiomer: Rodríguez, A. D. et al. Tetrahedron 1995, 51, 6869.
Disclaimer: Pathway from second structure purely my own guess based on very little evidence.
CladiellinsA AA
AA
a hypotheticalcladiellin
O3
8
1
11
4
3
8
1
11
4OH
OH
OH
OH
a hypotheticalcembranoid
3
8
1
11
4
OH
OH
OHHO
HO OH
OH
HO:-
structures reassigned-sclerophytin A, R=H
sclerophytin B, R=Ac
O
H
H
HH
OH
OR
OH
3
8
1
11
4
O3
8
1
11
4
O
H
HAcO
polyanthellin ABriareum polyanthes
[also isolated ent-polyanthellin A]
(alcyonin)structure misassigned - R=H
Sinularia flexibilisstructure reassigned - R=OH
due to enantioselective synthesis
O
H
H
HH
OR
OAc
OH
3
8
1
11
4
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
[o]
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
3
8
1
11
4
OH
OH
OHHO
O
-H3
8
1
11
4
OH
OH
OHHO
HOH
:B
-OH
then
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
Briarellin E, F enantioselective syntheses: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 ; isolation: Rodríguez, A. D. Chem. Pharm. Bull. 1995, 43, 1853; briarellin A original: Rodríguez, A. D. Tetrahedron 1995, 51, 6869; reassigned: Coll, J. C. Aust. J. Chem. 1989, 42, 1705; briarellin M-P: Rodríguez, A.
D. J. Nat. Prod. 2003, 66, 357.Disclaimer: Pathway from second structure purely my own guess based on very little evidence.
Cladiellins and AsbestininsA AA
AA
O
O
3 81
11
4
a hypotheticalasbestinin
a hypotheticalcladiellin
O3
8
1
11
4
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
3
8
1
11
4OH
OH
OH
OH
a hypotheticalcembranoid
3
8
1
11
4
OH
OH
OH
H+
HO HO OH
OH
HO:-
O
O
3 81R 11
4
briarellin FBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
O
O
O
3 81R 11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OH
O
O
3 81 11
4
structure reassigned - briarellin A, R1=H, R2=OOH
structure misassigned - briarellin A, R1=OH, R2=H
Briareum polyanthes
H
HR2O
H
O
R2
OCOC7H15R1
O
O
3 81 11
4
briarellin M, R1=H, R2=Acbriarellin N, R1=CH3, R2=Ac
briarellin O, R1=H, R2=COn-Prbriarellin P, R1=CH3, R2=COn-Pr
Briareum polyanthes
H
HR2O
H
OOR1
OH
H+
Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.Hypothetical biosynthetic pathway extrapolated from: Wahlberg, I.; Eklund, A.-M. Prog. Chem. Org. Nat. Prod. 1992, 60, 1-141 (review).
Disclaimer: Pathway from second structure purely my own guess based on very little evidence.
Cladiellins, Asbestinins and Sarcodictyins, Oh my!A AA
AA
O
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
3
8
1R
11
4H
H
OH
O
O
NN
O
a hypotheticalsarcodictyin
3
8
1
11
4
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
3
8
1
11
4OH
OH
OH
OH
a hypotheticalcembranoid
3
8
1
11
4
OH
OH
OHHO
O
CO2CH3
sarcodictyin A
3
8
1R
11
4H
H
OH
O
O
N
N
HO:-
OH
HOHO
[o]
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
3
8
1
11
4
OH
OH
OHHO
O
-H3
8
1
11
4
OH
OH
OHHO
HOH
:B
-OH
then
a hypotheticalcembranoid
(enzyme catalyzed, stepwise)
sarcophytol LSarcophyton glaucum
absolute stereochemistry
38
11
4
1
Aquariolide A: Andersen, R. J. Org. Lett. 2002, 4, 4085; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816;Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196.
Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate:
Higa, T. J. Nat. Prod. 2004, 67, 1368; Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
More Complex CembranoidsA AA
AA
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A
Brianthein A - Mosher: Kobayashi, M. Tetrahedron, 2001, 57, 8951.Juncenolide A - X-ray: Shen, Y. C. J. Nat. Prod. 2002, 65, 54.
Erythrolide S - Mosher: Andersen, R. J. Org. Lett. 2002, 4, 3515.Disclaimer: Second ring closure hypothesis without evidence or source other than my own brief consideration.
BriaranesA AA
AA
3 8
O 1
11
hypotheticalbriaran
4
18
9
OAc
1 8
9
3 8
1 11
4H
B:
OH
OH OH
OH
hypotheticalcembrane
OH
OH
3 8
1 11
4
OH
OH
3 8
1 11
4
OH
O
OH
H
OOH OAc
H
O
O n-Pr
O
OH
cyclobutenebriarein A absolute configuration by
analogy and proposed biogenesis
1S 38
erythrolide Sabsolute stereochemistry
by Mosher method
OO OAc
H
CO2CH3
38
AcO
HO
O
OAc
OAcO
OH
O OH
O
OAc
O
AcO
juncenolide Aabsolute stereochemistry
HO
O
Cl
OO
OAcH
3 8
brianthein A absolute stereochemistry
OAc
OAc
Hypothetical biosynthetic pathway proposed in: Wahlberg, I.; Eklund, A.-M. Prog. Chem. Org. Nat. Prod. 1992, 60, 1-141.Erythrolide L, aquarolides B, C, absolute stereochemistry of A: Andersen, R. J. Eur. J. Org. Chem. 2003, 3515.
Erythrolide A, B, V, aquariolide A: Andersen, R. J. Org. Lett. 2002, 4, 4085.
Coralloidoilide F: D'Ambrosio, M.A. et al. Helv. Chim. Acta, 1990, 73, 804-807; pinnatin A: Rodríguez, A. D. J. Org. Chem. 1998, 63(13), 4425-4432.Cembrene: Zhang, T. et al. Synthesis 2001, 3, 393; sinulochmodin C: Tseng, Y. J. et al. Org. Lett. 2005, 7(17), 3813-3816.
Sarcophytol L: Kobayashi, M.; Osabe, K. Chem. Pharm. Bull. 1989, 37, 1192-1196; Sclerophytin A: Paquette, L. A. Org. Lett. 2000, 2, 1879; Uchio, Y. Tetrahedron Lett. 1989, 30, 3331; Overmann, L. E. Org. Lett. 2001, 3, 135; Pennington, L. D. J. Am. Chem. Soc. 2001, 123, 9033; Paquette, L. A. J. Am. Chem. Soc. 2001, 123, 9021.
Erythrolide V: Andersen, R. J. et al. Eur. J. Org. Chem. 2003, 3515.Briarellin E enantioselective total synthesis: Overman, L. E. J. Am. Chem. Soc. 2003, 125, 6650 ; isolation: Rodríguez, A. D. Chem. Pharm. Bull. 1995, 43, 1853.
Minabein-4 absolute stereochemistry: (60) Molinski, J. Nat. Prod. 2004, 67, 2130; other identical isolate: Scheuer, P. J. Heterocycles 1996, 42, 325; Acetate: Higa, T. J. Nat. Prod. 2004, 67, 1368.Sarcodictyin A: Nakao, Y. et al. J. Nat. Prod. 2003, 66, 524.
Skeletal Termsexamples
A AA
AA
sclerophytin Atotal syntheses
O
3
8
111
4
OH
H
HOH
OH
O
O
3 81R
11
4
briarellin EBriareum aspestinum
enantioselective total synthesis
H
HOH
H
OCOC7H15
OHO
CO2CH3
(Z)-sarcodictyin ABellonella albiflora
absolute stereochemistry via transesterification to sarcodictyin A