Androstane Alkaloids from Musk of Moschus moschiferus.

Abstract

Musk, a dried preputial gland of the male musk deer (Moschus sp. Moschidae), 1) is one of the most popular and expensive Chinese drugs and has been used for cardiovascular stimulation, antiinflammation, and potentiation of badrenergic activity.2-4) Because all of this crude drug has been imported from other countries, distinguishing it from imitation musks that usually contain synthetic muscones is important in Korea. In the course of investigations into the characteristic steroids of musk, two androstane alkaloids (1, 2) were newly isolated from a natural source together with eight androstanoids and known cholestanoids, which had already been reported from the musk of M. moschiferus. 5,6) Compounds 1 and 2 were synthetically prepared by reaction of androst-4-ene-3,17-dione and testosterone with urea, although the their structural assignments were only given for protons. 7) We report here the identification of 1 and 2, and assignment of their NMR signals based on two-dimensional NMR analysis ( 1 H-1 H-COSY, HMQC, HMBC, and NOESY). Results and DiscussionCompound 1 3) suggested the presence of an amide group. From these 13 C-NMR data, 1 was considered to be a C 19 -ketosteroid having one substituent composed of one amino-, one imino-, and one carbonyl groups (i.e., an ureido group).8) This was further confirmed by two proton signals at d 6.21 and 6.83, which were not correlated with any carbons in the H 1 -detected multiple quantum coherence spectrum (HMQC). The entire structure was established by 1 H-1 H correlation spectroscopy (COSY) and 1 H-detected heteronuclear multiple-bond correlation spectrum (HMBC). In COSY, a multiplet methine proton at d 4.63 showed strong cross peaks with the protons at d 5.47 and 6.83. In HMBC, an NH proton at d 6.83 showed strong correlations with carbons at d 44.5, 120.9, and 159.3, and an olefinic methine proton at d 5.47 showed strong correlations with carbons at d 26.6 and 44.5 (Table 1). These results confirmed that a ureido group was present at the C-3 position of the androstane skeleton. 8,9) Recently, two steroidal alkaloids with the same partial structure of C-2 to C-5 [-CH 2 CH(NH)CHϭC-] were reported. Salignarine E [(20S)-2b-hydroxy-4b-acetoxy-5a,6a-epoxy-20-(dimethylamino)-3b -(tigloylamino)-pregnane], a pregnane-type alkaloid from Sarcococca saligna with a 3b-imino configuration, but NOE interactions between NH and H-2a/b and between H-1a and H-3/NH were not described.10) However, 22E,24R-3a -ureido-ergosta-4,6,8(14),22-tetraene from the fruit body of Chlorophyllum molybdites suggested a 3a-ureido configuration by NOE interaction between NH/H-1a. The stereochemistry of compound 1 at C-3 could be assigned to be the R configuration based on nuclear Overhouser effect spectroscopy (NOESY). The NOE interactions of H-1a at d 1.26 were unambiguously detected with H-9 (d 0.31) and NH (d 6.83), whereas H-3 (d 4.63) showed NOE interactions with H-4 (d 5.47), H-2 (d 1.75, 1.95) and NH (d 6.83), which suggested that the ureido group is a-oriented (Fig. 1). These spectral studies c...

The protective role of musk on salivary glands of mice exposed to chronic unpredictable mild stress

“…The protective role of musk on salivary glands might be attributable to its ability to reduce stress-induced elevation of the corticosterone level. Another explanation for the protective effect of musk may be its high content of steroids, which accounted for up to 14% of the musk examined in this study, similar to levels previously reported (33). The major steroid in musk is muscone, which is reported to have estrogenic activity (34), and sex steroid receptors including those for androgen, progesterone and estrogen receptor ß are expressed in the salivary glands (35).…”

Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts

“…The aimed structure was confirmed by 1 H NMR spectroscopy including 1 H- 1 H TOCSY and NOESY correlation spectra and comparison to literature data,10 with the NOE interactions outlining the desired stereochemistry at C-3: 1 H NMR (pyridine-d 5 , 600 MHz): δ (ppm)=0.31 (m, 1H, H-9), 0.61 (m, 1H, H-7), 0.76 (s, 3H, H-18), 0.85 (s, 3H, H-19), 0.91 (m, 1H, H-14), 1.11 (m, 1H, H-12), 1.15 (m, H-11), 1.27 (m, 1H, H-1 ax. ), 1.34 (m, 1H, H-11), 1.36 (m, 1H, H-8), 1.39 (m, 1H, H-1 eq.…”

“…These herbal products were shown to contain ephedrine and its structural analogues such as norephedrine, pseudoephedrine and cathine that would lead to a positive test result if urinary threshold levels are exceeded. Sources and applications of steroid hormone-containing remedies were rarely reported; however, few articles were published particularly concerning the composition6 7 and use of musk pod and its extracts as TCM in cases of health conditions necessitating cardiovascular and/or β-adrenergic stimulation,8 anti-inflammatory therapeutics9 or androgenic hormone intervention 6 7 10. Musk is the dried secretion from the preputial follicles of the male musk deer, which are located in a small sac (resulting from an infolding of the skin) in close proximity to the preputial orifice (figure 1A).…”

Therapeutic Potential of Pien-Tze-Huang: A Review on Its Chemical Composition, Pharmacology, and Clinical Application

“…The results showed that Radix et Rhizoma Notoginseng mainly contains protopanaxadiol-type (e.g., notoginsenoside R1 and ginsenosides Re, Rf, Rg1, and Rg2) and protopanaxatriol-type ginsenosides (e.g., ginsenosides Rb1, Rc, Rd, and Rg3), which are considered its main bioactive compounds [6]. Moschus mainly contains macrocyclic ketones (e.g., muscone) and steroids (e.g., androsterone), which possess extensive biological activities [7]. Calculus Bovis mainly contains bile acids and their glycine or taurine conjugates, such as cholic acid, deoxycholic acid, chenodeoxycholic acid, hyodeoxycholic acid, and ursodeoxycholic acid, which are supposed to be its main characteristic and bioactive compounds [8].…”