**2.13. Congeners of** *Xylaria* **sp.: structural interrelations**

Endophytic fungi are reported to produce a number of bioactive metabolites and serve as an excellent source of highly oxygenated compounds which are likely to be potential drugs and also for the applications in crop science. The fungi belonging to genus *Xylaria* produces plethora of biologically related and structurally fascinating cadinenic and eudesmanic sesquiterpenes.

Liu and coworkers [33] reported isolation of highly oxygenated cadinane based compounds, three new xylaric acid A **65**, xylaric acid B **66** and xylaric acid C **67** and nine known compounds xylaric acid D **68**, heptelidic acid (avocetlin) [34] **69** hydroheptelidic acid **70**, gliocladic acid **71**, chlorheptelidic acid **72**, trichoderonic acid A **73**. The structure assignments are based on extensive spectral analysis. All these congeners belong to cadinane or seco-cadinane group of sesquiterpenes (**Figure 8**). The stereochemistry at C6 and C7 is unchanged for all the metabolites where C1 remains same for **66**, **67**, **69**, **70**, **72** and **73** and changes for **65**, **68** and **71**.

Recent Developments in Selected Sesquiterpenes: Molecular Rearrangements, Biosynthesis… http://dx.doi.org/10.5772/intechopen.74998 105

**Scheme 21.** Proposed new consolidated mechanism for the biosynthesis of valerenadiene **47**.

Bicyclogermacrene **36** appears also to be an intermediate in the biosynthesis of related set of sesquiterpene with different stereochemistry found in *Valeriana officinalis*, including tamariscene **60**, pacifigorgiol **61** and (+)-pacifigorgia-1,10-diene **62** (**Scheme 20**). In this scheme also the key reaction is again cyclopropylcarbinyl cation-cyclopropylcarbinyl cation rearrange-

Based on the results of three groups [4, 30, 31] a new consolidated mechanism for the biosynthesis of valerenadiene **47** from FPP *via* bicyclogermacrene **36** through alloaromadendryl cation **63** and CCR is presented which also explains formation of alloaromadendrene **64** (**Scheme 21**)

**Scheme 20.** Biosynthetic pathway of tamariscene **60**, pacifigorgiol **61** and (+)-pacifigorgia-1,10-diene **62** from

Endophytic fungi are reported to produce a number of bioactive metabolites and serve as an excellent source of highly oxygenated compounds which are likely to be potential drugs and also for the applications in crop science. The fungi belonging to genus *Xylaria* produces plethora of biologically related and structurally fascinating cadinenic and eudesmanic sesquiterpenes. Liu and coworkers [33] reported isolation of highly oxygenated cadinane based compounds, three new xylaric acid A **65**, xylaric acid B **66** and xylaric acid C **67** and nine known compounds xylaric acid D **68**, heptelidic acid (avocetlin) [34] **69** hydroheptelidic acid **70**, gliocladic acid **71**, chlorheptelidic acid **72**, trichoderonic acid A **73**. The structure assignments are based on extensive spectral analysis. All these congeners belong to cadinane or seco-cadinane group of sesquiterpenes (**Figure 8**). The stereochemistry at C6 and C7 is unchanged for all the metabolites

where C1 remains same for **66**, **67**, **69**, **70**, **72** and **73** and changes for **65**, **68** and **71**.

replace alloaromadendryl cation with allo-aromadendryl cation.

**2.13. Congeners of** *Xylaria* **sp.: structural interrelations**

bicyclogermacrene **36**.

104 Terpenes and Terpenoids

ment (CCR) with this time with a different stereoisomer.

**Figure 8.** Structural interrelations among the congeners of *Xylaria* sp. and the sequence of formation of isolated metabolites **65**–**73**.

Knowing the absolute stereochemistry of the congeners and their fungal origin, they belong to the "antipodal" set of compounds and they can be regarded as a result of extensive oxidative reactions of (−)-γ-cadinene **74**. Recently, Rabe *et al.* [35] have reported isolation of several sesquiterpenes including (−)-γ-cadinene, [α]D-32.3° by incubation of FPP with six purified bacterial terpene cyclases. The results were further supported by labeling experiments with 13C labeled isotopomers of FPP. Interestingly, antipodal cadinenic sesquiterpenes with known absolute configurations have been isolated from Indian vetiver oil (*Vetiveria zizanioides*) [36]. Isolation of (−)-γ-cadinene **74**, khusinol **75** and khusinol oxide **76** could be regarded as the precursors for the metabolites of *Xylaria* sp. A very clean sequence indicating a plausible order of formation of *Xylaria sp.* metabolites associated with the termite nest is presented (**Scheme 22**). We believe that this presentation will be useful while investigating the biosynthetic pathways using isotopic labeling studies.

**Acknowledgements**

**Author details**

India

**References**

24273843

10.1021/jo101691n

Shashikumar K. Paknikar<sup>1</sup>

We wish to dedicate this review to Professor R. B. Bates on his retirement from Research. We thank Dr. Asha D'Souza, Prof. Shailesh Shah and Rahul Chowgule for their valuable help in

Recent Developments in Selected Sesquiterpenes: Molecular Rearrangements, Biosynthesis…

http://dx.doi.org/10.5772/intechopen.74998

107

\* and Kamlesh Pai Fondekar<sup>2</sup>

2 Deccan Fine Chemicals, Technology and Engineering, Santa Monica Works, Corlim, Goa,

[1] Paknikar SK, Kamounah FS, Hansen PE, Wadia MS. Multi-step rearrangement mechanism for acetyl cedrene to the hydrocarbon follower. Chemistry of Natural Compounds.

[2] Nabeta K, Ara Y, Aoki Y, Miyake M. Biosynthesis of monoterpenes and sesquiterpenes in *Larix leptolepis* Callus from deuterated mevalonates. Journal of Natural Products.

[3] Blagg BSJ, Jarstfer DH, Rogers DH, Poulter CD. Recombinant squalene synthase. A mechanism for the rearrangement of presqualene diphosphate to squalene. Journal of

[4] Paknikar SK, Kadam SH, Ehrlich AL, Bates RB. Alternate biosynthesis of valerenadiene and related sesquiterpenes. Natural Product Communications. 2013;**8**:1195-1196. PMID:

[5] Morales PA, Amaro-Luis JM, Kutateladze AG. Structure determination and mechanism of formation of a seco-moreliane derivative supported by computational analysis. Journal of Natural Products. 2017;**80**:1210-1214. DOI: 10.1021/acs.jnatprod.7b00041

[6] Joseph-Nathan P, Reyes-Trejo B, Morales-Rios MS. Molecular rearrangements of (−)-modhephene and (−)-isocomene to a (−)-triquinane. Journal of Organic Chemistry.

[7] Uroos M, Lewis W, Blake AJ, Hayes CJ. Total synthesis of (+)-cymbodiacetal: A re-evaluation of the biomimetic route. Journal of Organic Chemistry. 2010;**75**:8465-8470. DOI:

the American Chemical Society. 2002;**124**:8846-8853. DOI: 10.1021/ja020411a

1 Siddharth Chemicals, Kundaim Industrial Estate, Kundaim, Goa, India

providing many research articles required for this review.

\*Address all correspondence to: skpakni@yahoo.co.in

2017;**53**:1-4. DOI: 10.1007/s10600-017-2085-1

1990;**53**:1241-1248. DOI: 10.1021/np50071a016

2006;**71**:4411-4417. DOI: 10.1021/jo060258t

**Scheme 22.** Proposed plausible order of formation of *Xylaria* sp. metabolites from FPP.
