Platinum- and Gold-Catalyzed Cycloisomerization Reactions of Hydroxylated Enynes

Mamane, Victor; Gress, Tobias; Krause, Helga; Fürstner, Alois

doi:10.1021/ja048094q

Cited by 540 publications

(225 citation statements)

References 17 publications

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“…Because the 3-hydroxyl only in the cis isomer is close through space proximity to the C-6 CH2 group, the corresponding protons are shifted significantly to low field in the 1 H NMR spectrum (cis, 0.65 ppm for 6a and 0.57 ppm for 6b; trans, 1.08 ppm for 6a and 0.85 ppm for 6b). The assignment agrees with data published by Ohloff et al (1966) and Mamane et al (2004). (+)-cis-Sabinol structure was determined by 1 H and 13 C NMR.…”

Section: Assignment Of (+)-Sabinol Stereochemistrysupporting

confidence: 88%

The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

et al. 2015

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Western redcedar (WRC; Thuja plicata) produces high amounts of oxygenated thujone monoterpenoids associated with resistance against herbivore feeding, particularly ungulate browsing. Thujones and other monoterpenoids accumulate in glandular structures in the foliage of WRC. Thujones are produced from (+)-sabinene by sabinol and sabinone. Using metabolite analysis, enzyme assays with WRC tissue extracts, cloning, and functional characterization of cytochrome P450 monooxygenases, we established that transsabin-3-ol but not cis-sabin-3-ol is the intermediate in thujone biosynthesis in WRC. Based on transcriptome analysis, full-length complementary DNA cloning, and characterization of expressed P450 proteins, we identified CYP750B1 and CYP76AA25 as the enzymes that catalyze the hydroxylation of (+)-sabinene to trans-sabin-3-ol. Gene-specific transcript analysis in contrasting WRC genotypes producing high and low amounts of monoterpenoids, including a glandless low-terpenoid clone, as well as assays for substrate specificity supported a biological role of CYP750B1 in a-and b-thujone biosynthesis. This P450 belongs to the apparently gymnosperm-specific CYP750 family and is, to our knowledge, the first member of this family to be functionally characterized. In contrast, CYP76AA25 has a broader substrate spectrum, also converting the sesquiterpene farnesene and the herbicide isoproturon, and its transcript profiles are not well correlated with thujone accumulation.

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Section: Assignment Of (+)-Sabinol Stereochemistrysupporting

confidence: 88%

The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

et al. 2015

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“…Under these conditions,t wo separable epimers (6 and 6'')w ere formed in a4 :1 ratio (Scheme 6). Surprisingly,a lthough 1 HNMR of the major isomer 6 was identical to that reported for anhydrocannabimovone,very significant differences were observed in the 13 CNMR spectrum. [20] Furthermore,t he optical rotation of 6 ([a] 22 D =+40.68 8 (c = 0.29, CHCl 3 )) was very different to that reported ([a] 22 D = À178 8 (c = 0.02, CHCl 3 )).…”

supporting

confidence: 64%

Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

2016

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The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of ah ighly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone.The herbaceous plant Cannabis sativa has been used in medicine for centuries and still attracts significant interest due to the biological and pharmaceutical activity of many of its metabolites.[1] More than 60 compounds,k nown as cannabinoids (a group of C 21 terpenophenolic compounds), are exclusively found in Cannabis sativa.[2] Owing to the development of synthetic cannabinoids, [3, 4] theunique components of Cannabis sativa are known as phytocannabinoids.T he most abundant compound is D 9-tetrahydrocannabinol (THC, 1; Figure 1), which shows interesting pharmacological activity as an analgesic,a ntiemetic,a nd appetite stimulant, among others,b esides its well-known psychotropic effects.[5] Several total syntheses of 1 have been accomplished to date. [6] Cannabidiol (CBD, 2)isanother important phytocannabinoid with great potential as ad rug [7] since it modulates the undesired effects of THC when they are administrated together. [8] As tructurally different cannabinoid named cannabimovone (3)h as recently been isolated by the groups of Taglialatela-Scafati and Appendino from an onpsychotropic variety of hemp (Cannabis sativa L.;F igure 1). [9] In their attempt at preparing 3 from CBD (2)t hrough an intramolecular aldol reaction of keto aldehyde 4 under mild acidic conditions,the product of dehydration (5)was formed instead (Scheme 1). Under basic conditions,t he novel cannabinoid anhydrocannabimovone (6)w as directly formed through an intramolecular oxy-Michael addition of one of the phenol groups to the intermediate enone.Synthetic 6 was found to be active against metabotropic and ionotropic cannabinoid receptors,s howing as imilar biological profile to THC, whereas cannabimovone (3)h as affinity only for ionotropic receptors. [9] Theunprecedented abeo-menthane terpenoid structure of cannabimovone (3)i ncludes ad ensely functionalized cyclopentane with four contiguous stereocenters.T he novel structure of 3,c oupled with its lability towards dehydration under acidic or basic conditions and the interesting biological profiles of both 3 and 6,i nspired us to develop at otal synthesis that could allow access to aw ide variety of Scheme 1. Synthesis of anhydrocannabimovone( 6)f rom cannabidiol (CBD, 2).[9][*] Dr.J .C arreras, M.

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“…Diene 34 was converted to tricyclic pyrrole intermediate 35 in an 11-step sequence. Since 35 was previously converted to roseophilin (36), this represented a formal synthesis of this alkaloid (Scheme 8).…”

Section: Scheme 2 a C H T U N G T R E N N U N G (Pphmentioning

confidence: 99%

Gold and Platinum Catalysis of Enyne Cycloisomerization

2006

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This account provides a comprehensive overview of the development of gold and platinum catalysis of the enyne cycloisomerization. The use of these soft, alkynophilic metals enables mild, chemoselective and efficient transformations of a variety of readily available acyclic enynes to a wide range of synthetically useful carbocyclic and heterocyclic products. The review is organized according to diverse structural types of enynes that undergo skeletal cycloisomerizations. The account begins with an overview of transformations of primarily 1,6-enynesheptenes. This section is followed by the discussion of cycloisomerizations of 1,5-enynes, which enable a rapid access to a range of other cyclic products, including bicycloA C H T U N G T R E N N U N G [3.1.0]hexenes, cyclohexadienes, heterobicycloalkenes, methylenecyclopentenes, naphthalenes and methyleneindenes. In addition, the [3,3] rearrangement of 1,5-enynes provides efficient access to the corresponding allenes. The account concludes with an overview of the most recent studies on gold-and platinum-catalyzed cycloisomerizations of 1,4-and 1,3-enynes. Due to the rapidly increasing interest in this area during the past three to five years, we believe that this review provides a timely and comprehensive discussion of the development gold-and platinum-catalyzed cycloisomerization starting from the initial pioneering investigations to the latest advances in the field. A significant emphasis is placed on the mechanistic discussion of the observed manifolds of skeletal reorganizations.

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Platinum- and Gold-Catalyzed Cycloisomerization Reactions of Hydroxylated Enynes

Cited by 540 publications

References 17 publications

The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

The Gymnosperm Cytochrome P450 CYP750B1 Catalyzes Stereospecific Monoterpene Hydroxylation of (+)-Sabinene in Thujone Biosynthesis in Western Redcedar

Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

Gold and Platinum Catalysis of Enyne Cycloisomerization

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