Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • br Introduction Fungi are an

    2023-01-24


    Introduction Fungi are an inexhaustible source of natural products mainly due to their wide distribution in the nature, estimated to range from 1.5 to 5.1 million species in the world [1]. Secondary metabolites from fungi represent a substantial fraction of drugs and drug models in pharmaceutical industries, including antibiotics, statins and immunosuppressant [2], [3]. Fungal biosynthetic routes used to produce secondary metabolites are also useful to undertake structural modifications in xenobiotic compounds. Biotransformation is a tool that has been extensively used to prepare derivatives from trachylobane diterpenes. Trachyloban-19-oic Cy5 amine (non-sulfonated) australia (1), a natural diterpene found in plants of different genera such as Croton[4], Xylopia[5], [6], Arctopus[7], Iostephane[8], and Helianthus[9], is a promisor substrate for preparing new bioactive derivatives. Biotransformation by fungi has attracted great interest to the pharmaceutical, chemical and food industries due of numerous advantages, mainly the capacity of performing chemo-, regio- and enantio-selective reactions [10], [11]. In trachylobane diterpenes, biotransformation most commonly leads to hydroxylation and skeleton rearrangement. Hydroxylation has been accomplished at several positions such as C-7β and C-17 [12] and C-11β[13] using Rhizopus stolonifer, C-1α and C-17 using Rhizopus arrhizus[14], C-19 using Gibberella fujikuroi[15], and at C-7β using Mucor plumbeus (Fig. 1) [16]. In addition, rearrangements of trachylobane into kauranes diterpenes by R. stolonifer were described [12], [13]; in this case, the covalent bond between C-12 and C-16 is disrupted, with formation of a C-16 tertiary carbocation, which is subsequently hydrated. Thus, trachylobane skeleton is pointed as the precursor of ent-kaur-1l-ene derivatives [9]. Another rearrangement found in the literature from trachylobane diterpenes lead to the formation of trachylobagibberellins by G. fujikuroi[9], [17]. Formation of trachylobagibberellins involves an oxidation of C-19 followed by hydroxylation at C-7 and contraction of ring B with C-7 extrusion. In the biotransformation of ent-trachyloban-18-oic acid by R. arrhizus another type of rearrangement was described, in which the bond between C-13 and C-16 was disrupted and a new bond was created between C-11 and C-13, followed by formation a double bond between C-15 and C-16 [14]. In a previous work [16], trachyloban-19-oic acid (1) and derivatives showed acetylcholinesterase inhibition, raising our interest to prepare further derivatives for biological screening, since new drug leads for treatment of Alzheimer’s disease are very welcome worldwide. Therefore, we report herein the biotransformation of trachyloban-19-oic acid (1) by S. racemosum into one known and two new products: 17-hydroxytrachyloban-19-oic acid (2), trachyloban-17,19-dioic acid (3) and ent-16β,17-dihydroxykaur-11-en-19-oic acid (4), respectively. S. racemosum was chosen due to its fast growth and poor secondary metabolism, which are useful features in biotransformation experiments. Substrate 1 and products 2–4 were screened for acetylcholinesterase inhibitory activity.
    Results and discussion Incubation of trachyloban-19-oic acid (1) with the fungus S. racemosum led to the isolation of three compounds 2–4 (Fig. 2). These compounds were isolated by successive purifications by column chromatography, and their structures were identified by 1H and 13C NMR combined with 1D and 2D NMR techniques. Compound 2 was identified as 17-hydroxytrachyloban-19-oic acid, which have already been obtained from biotransformation of 1 by R. stolonifer[12]. Compounds 3 and 4 are hydroxylation and rearrangement products, respectively, and to the best of our knowledge, these compounds have not been described before. Compound 2 (13 mg) was purified as an amorphous, colourless powder. The molecular formula was established as C20H30O3 by HRESIMS, associated to 1H and 13C NMR spectroscopic data (Table 1). IR spectrum showed bands for hydroxyl (3427 cm−1) and carbonyl (1705 cm−1) groups. 13C NMR spectrum exhibited twenty signals, two of them assigned for C-18 and C-20 methyl groups (δC 29.6 and 13.2, respectively), and five signals of quaternary carbons, including C-19 carboxyl group (δC 180.3). 1H NMR spectrum showed signals at δH 1.31 and 1.10 (H-18 and H-20 respectively), and a signal at δH 3.89, assigned to H-17 (δC 66.8). H-12 signal (δH 1.02) in compound 2 was displaced when compared to H-12 signal (δH 0.55) of starting material 1. HMBC spectrum showed correlations between the signal of H-17 and C-16, C-15, C-13 and C-12, confirming that hydroxylation occurred at C-17. Therefore, compound 2 was identified as 17-hydroxytrachyloban-19-oic acid. This compound has been previously reported as a biotransformation product of trachyloban-19-oic acid by R. stolonifer[12].