Cyclic Guanidine Compounds from Toxic Newts Support the Hypothesis that Tetrodotoxin is Derived from a Monoterpene

The biosynthesis of tetrodotoxin (TTX), a potent neurotoxin consisting of a 2,4‐dioxaadamantane skeleton and a guanidine moiety, is an unsolved problem in natural product chemistry. Recently, the first C5–C10 directly bonded TTX analogue, 4,9‐anhydro‐10‐hemiketal‐5‐deoxyTTX, was obtained from toxic newts and its carbon skeleton suggested a possible monoterpene origin. On the basis of this hypothesis, screening of predicted biosynthetic intermediates of TTX was performed using two MS‐guided methods. Herein, five novel cyclic guanidine compounds from toxic newts are reported which commonly contain a cis‐fused bicyclic structure including a six‐membered cyclic guanidine. These structures could be biosynthetically derived from geranyl guanidine through oxidation, cyclization, and/or isomerization steps. LC–MS analysis confirmed the widespread distribution of the five novel compounds in toxic newt species. These results support the hypothesis that TTX is derived from a monoterpene.     

Total Synthesis of (−)‐Tetrodotoxin and 11‐norTTX‐6(R)‐ol

The enantioselective total synthesis of (−)‐tetrodotoxin [(−)‐TTX] and 4,9‐anhydrotetrodotoxin, which are selective blockers of voltage‐gated sodium channels, was accomplished from the commercially available p ‐benzoquinone. This synthesis was based on efficient stereocontrol of the six contiguous stereogenic centers on the core cyclohexane ring through Ogasawara's method, [3,3]‐sigmatropic rearrangement of an allylic cyanate, and intramolecular 1,3‐dipolar cycloaddition of a nitrile oxide. Our synthetic route was applied to the synthesis of the tetrodotoxin congeners 11‐norTTX‐6(R )‐ol and 4,9‐anhydro‐11‐norTTX‐6(R )‐ol through late‐stage modification of the common intermediate. Neutral deprotection at the final step enabled easy purification of tetrodotoxin and 11‐norTTX‐6(R )‐ol without competing dehydration to their 4,9‐anhydro forms.     

Eremosides A – C,New Iridoid Glucosides from Eremostachys loasifolia

Eremosides A–C ( 1 – 3 ), three new iridoid glucosides, were isolated from the AcOEt‐soluble fraction of the EtOH extract of the whole plant of Eremostachys loasifolia, along with buddlejoside B ( 4 ), 10‐O‐benzoylcatalpol ( 5 ), and pakiside A ( 6 ) reported for the first time from this species. The structures of these compounds were elucidated by spectroscopic data including 2D‐NMR, FAB‐MS, ESI‐MS, as well as by acid and basic hydrolyses.     

Synthesis and Base Pairing Properties of 1′,5′‐Anhydro‐L‐Hexitol Nucleic Acids (L‐HNA)

Oligonucleotides composed of 1′,5′‐anhydro‐arabino‐hexitol nucleosides belonging to the L series (L ‐HNA) were prepared and preliminarily studied as a novel potential base‐pairing system. Synthesis of enantiopure L ‐hexitol nucleotide monomers equipped with a 2′‐(N⁶‐benzoyladenin‐9‐yl) or a 2′‐(thymin‐1‐yl) moiety was carried out by a de novo approach based on a domino reaction as key step. The L oligonucleotide analogues were evaluated in duplex formation with natural complements as well as with unnatural sugar‐modified oligonucleotides. In many cases stable homo‐ and heterochiral associations were found. Besides T_m measurements, detection of heterochiral complexes was unambiguously confirmed by LC‐MS studies. Interestingly, circular dichroism measurements of the most stable duplexes suggested that L ‐HNA form left‐handed helices with both D and L oligonucleotides.     

Synthesis of a new 2‐amino‐glycan,poly‐(1→6)‐α‐D‐mannosamine,by ring‐opening polymerization of 1,6‐anhydro‐mannosamine derivatives

A stereoregular 2‐amino‐glycan composed of a mannosamine residue was prepared by ring‐opening polymerization of anhydro sugars. Two different monomers, 1,6‐anhydro‐2‐azido‐mannose derivative ( 3 ) and 1,6‐anhydro‐2‐(N, N‐dibenzylamino)‐mannose derivative ( 6 ), were synthesized and polymerized. Although 3 gave merely oligomers, 6 was promptly polymerized into high polymers of the number‐average molecular weight (M_n) of 2.3 × 10⁴ to 2.9 × 10⁴ with 1,6‐α stereoregularity. The differences of polymerizability of 3 and 6 from those of the corresponding glucose homologs were discussed. It was found that an N‐benzyl group is exceedingly suitable for protecting an amino group in the polymerization of anhydro sugars of a mannosamine type. The simultaneous removal of O‐ and N‐benzyl groups of the resulting polymers was achieved by using sodium in liquid ammonia to produce the first 2‐amino‐glycan, poly‐(1→6)‐α‐D ‐mannosamine, having high molecular weight through ring‐opening polymerization of anhydro sugars.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Cationic and mesoionic 1,3‐thiazolo‐[3,2‐c]quinazoline derivatives

4‐Allylthio‐2‐arylquinazolines 4a–c undergo cyclization by action of bromine to furnish 5‐aryl‐3‐bromomethyl‐2,3‐dihydrothiazolo[3,2‐c]quinazolin‐4‐ium bromides 5a–c . Compounds 5a–c undergo ring opening by action of water under acid catalysis to afford the corresponding dibromide derivatives 6a–c . Bromination of 3‐allyl‐2‐aryl‐4(3H)quinazolinethiones 7a–c leads to 5‐aryl‐2‐bromomethyl‐2,3‐dihydrothiazolo[3,2‐c]quinazolin‐4‐ium bromides 8a–c . However, anhydro‐3‐hydroxy‐5‐aryl‐1,3‐thiazolo[3,2‐c]quinazolin‐4‐ium hydroxide 10a–c were prepared by the cyclodehydration of the corresponding thioglycolic acids 9a–c with Ac₂O. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:576–580, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10148     

Synthesis of Branched Ribo‐Polysaccharides with Defined Structures by Ring‐Opening Polymerization of 1,4‐Anhydro Ribo‐Disaccharide Monomer

Ring‐opening polymerization of a new 1,4‐anhydro‐disaccharide monomer, 1,4‐anhydro‐2‐O‐benzyl‐3‐O‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D ‐galactopyranosyl)‐α‐D ‐ribopyranose, which was prepared by the glycosylation of 1,4‐anhydro‐2‐O‐benzyl‐α‐D ‐ribopyranose with 2,3,4,6‐tetra‐O‐acetyl‐1‐O‐trichloroacetimidoyl‐α‐D ‐galactopyranose, was performed for the first time with boron trifluoride etherate to give stereoregular branched ribofuranans having high molecular weights of M̄_n = 43.0×10³ and positive specific rotation of [α]_D²⁵ = +25.1 deg·dm^–1· g^–1·cm³. The repalcement of the benzyl group by a hydroxyl group gave stereoregular 1,5‐α‐D ‐ribofuranans having a β‐D ‐galactopyranose branch in every repeating unit. The copolymerization of the ribo‐disaccharide monomer with 1,4‐anhydro‐2,3‐di‐O‐benzyl‐α‐D ‐ribopyranose was also carried out to afford stereoregular 1,5‐α‐D ‐ribofuranans having randomly distributed galactopyranose branches on the main chain.     

Syntheses of β‐C(1→3)‐Glucopyranosides of 2‐ and 4‐Deoxy‐D‐hexoses

The Oshima? Nozaki (Et₂AlI) condensation of isolevoglucosenone ( 4 ) with 2,6‐anhydro‐3,4,5,7‐tetra‐O‐benzyl‐D ‐glycero‐D ‐gulo‐heptose ( 5 ) gave an enone 6 that was converted with high stereoselectivity to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐2,3‐dideoxy‐D ‐arabino‐hexose ( 1 ; 1 : 1 mixture of α‐ and β‐D ‐pyranose), and to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐2,3‐dideoxy‐D ‐lyxo‐hexose ( 2 ; 2.7 : 1.4 : 1.0 : 1.4 mixture of α‐D ‐furanose, β‐D ‐furanose, α‐D ‐pyranose, and β‐D ‐pyranose). The Oshima? Nozaki (Et₂AlI) condensation of levoglucosenone ( 17 ) with aldehyde 5 gave an enone 18 that was converted with high stereoselectivity to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐3,4‐dideoxy‐α‐D ‐arabino‐hexopyranose ( 3 ; single anomer).     

Synthesis of Novel Bromo-substituted Flavone-like Troponoid Compounds from Oxidation Cyclization of 3-Cinnamoyl-5,7-dibromotropolones Using I2/DMSO/H2SO4 System

A convenient method to obtain a series of bromo‐substituted flavone‐like troponoid compounds 6,8‐dibromo‐2‐arylcyclohepta[b]pyran‐4,9‐diones 3a–3s by oxidation cyclization of the readily available intermediates 3‐cinnamoyl‐5,7‐dibromotropolones 2a–2s using I₂/DMSO/H₂SO₄ system was realized. Compounds 2a–2s were obtained from the aldol reaction of 3‐acetyl‐5,7‐dibromotropolone 1 with various benzaldehydes. Compounds 2a–2s and 3a–3s are novel and their structures were supported by IR, ¹H NMR, MS and elemental analyses.     

Design and Synthesis of Aminoglycoside Antibiotics to Selectively Target 16S Ribosomal RNA Position 1408

The glucopyranosyl moiety (ring I) of paromomycin was modified in a search for novel aminoglycoside antibiotics. The key intermediates were the 4′,6′‐O‐benzylidenated N‐Boc derivative 3 and the azido analogue 18 . The bromobenzoates 4 and 19 were prepared by treating the benzylidene acetals 3 and 18 , respectively, with N‐bromosuccinimide (NBS), and the diol 8 was obtained by hydrogenolysis of 3. The C(6′)‐deoxy derivative 5 was obtained from 4 by treatment with Bu₃SnH. Selective fluorodehydroxylation of 8 gave the fluoro derivative 9. The pseudotrisaccharide 13 was obtained by reductive fragmentaion of the iodo compound 12 obtained from the bromobenzoate 4 . The 3′,6′‐anhydro derivative 20 was obtained upon deacetylation of 19. Standard deprotection gave the C(6′)‐deoxy compound 7 , the fluoro compound 11 , the pseudotrisaccharide 15 , and the 3′,6′‐anhydro‐paromomycin 22 . As compared to paromomycin, the C(6′)‐deoxy and fluorodeoxy derivatives 7 and 11 showed a lower activity against both wild type 1408A and 1408G mutant ribosomes. A lower activity was also found for the 3′,6′‐anhydro derivative 22 and for the pseudotrisaccharide 15 .     

One‐pot Synthesis of a 3,4,5‐Triaryltriazole from the Subsitituted 1,3,4‐Oxadiazole: Crystal Structures Characterization

Two heterocyclic compounds, 2‐(p‐bromophenyl)‐5‐(2‐pyridyl)‐1,3,4‐oxadiazole ( 1 ) and 3‐(p‐bromophenyl)‐4‐phenyl‐5‐(2‐pyridyl)‐1,2,4‐triazole ( 2 ) were successfully synthesized and characterized by UV–vis, FTIR, ¹H NMR, ESI‐MS spectra, elemental analysis, and single crystal X‐ray crystallography. The structural analysis indicates that 1 is almost a planar molecule but 2 not. The crystal structure of 1 is stabilized by two kinds of intermolecular π–π interactions and two types of intermolecular C–H···N hydrogen bonds, whereas 2 by three kinds of C–H···π interactions and three types of intermolecular C–H···N hydrogen bonds. Additional, 2 can be prepared directly from 1 in an aniline solution at 190°C in a yield of 70%.     

Stereoselective Synthesis of 8‐Oxabicyclo[3.2.1]octane‐2,3,4,6,7‐pentols and Total Asymmetric Synthesis of 2,6‐Anhydrohepturonic Acid Derivatives and of β‐C‐manno‐Pyranosides Suitable for the Construction of (1→3)‐C,C‐Linked Trisaccharides

Enantiomerically pure (+)‐(1S,4S,5S,6S)‐6‐endo‐(benzyloxy)‐5‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((+)‐ 5 ) and its enantiomer (−)‐ 5 , obtained readily from the Diels‐Alder addition of furan to 1‐cyanovinyl acetate, can be converted with high stereoselectivity into 8‐oxabicyclo[3.2.1]octane‐2,3,4,6,7‐pentol derivatives (see 23 – 28 in Scheme 2). A precursor of them, (1R,2S,4R,5S,6S,7R,8R)‐7‐endo‐(benzyloxy)‐8‐exo‐hydroxy‐3,9‐dioxatricyclo[4.2.1.0^2,4]non‐5‐endo‐yl benzoate ((−)‐ 19 ), is transformed into (1R,2R,5S, 6S,7R,8S)‐6‐exo,8‐endo‐bis(acetyloxy)‐2‐endo‐(benzyloxy)‐4‐oxo‐3,9‐dioxabicyclo[3.3.1]non‐7‐endo‐yl benzoate ((−)‐ 43 ) (see Scheme 5). The latter is the precursor of several protected 2,6‐anhydrohepturonic acid derivatives such as the diethyl dithioacetal (−)‐ 57 of methyl 3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐D ‐glycero‐D ‐galacto‐hepturonate (see Schemes 7 and 8). Hydrolysis of (−)‐ 57 provides methyl 3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐D ‐glycero‐D ‐galacto‐hepturonate 48 that undergoes highly diastereoselective Nozaki‐Oshima condensation with the aluminium enolate resulting from the conjugate addition of Me₂AlSPh to (1S,5S,6S,7S)‐7‐endo‐(benzyloxy)‐6‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐8‐oxabicyclo[3.2.1]oct‐3‐en‐2‐one ((−)‐ 13 ) derived from (+)‐ 5 (Scheme 12). This generates a β‐C‐mannopyranoside, i.e., methyl (7S)‐3,5‐di‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐7‐C‐[(1R,2S,3R,4S,5R,6S,7R)‐6‐endo‐(benzyloxy)‐7‐exo‐{[(tert‐butyl)dimethylsilyl]oxy}‐4‐endo‐hydroxy‐2‐exo‐(phenylthio)‐8‐oxabicyclo[3.2.1]oct‐3‐endo‐yl]‐L ‐glycero‐D ‐manno‐heptonate ((−)‐ 70 ; see Scheme 12), that is converted into the diethyl dithioacetal (−)‐ 75 of methyl 3‐O‐acetyl‐2,6‐anhydro‐4,5‐dideoxy‐4‐C‐{[methyl (7S)‐3,5,7‐tri‐O‐acetyl‐2,6‐anhydro‐4‐O‐benzoyl‐L ‐glycero‐D ‐manno‐heptonate]‐7‐C‐yl}‐5‐C‐(phenylsulfonyl)‐L ‐glycero‐D ‐galacto‐hepturonate ( 76 ; see Scheme 13). Repeating the Nozaki‐Oshima condensation to enone (−)‐ 13 and the aldehyde resulting from hydrolysis of (−)‐ 75 , a (1→3)‐C,C‐linked trisaccharide precursor (−)‐ 77 is obtained.     

Monoterpenoids from the Fruit of Gardenia jasminoides

Eight new monoterpenoids, jasminoside J ( 1 ), jasminoside K ( 2 ), 6′‐O‐trans‐sinapoyljasminoside B ( 3 ), 6′‐O‐trans‐sinapoyljasminoside L ( 4 ), jasminosides M–P ( 5 – 8 ), together with three known analogues, jasminoside C ( 9 ), jasminol E ( 10 ), and sacranoside B ( 11 ), were isolated from the fruit of Gardenia jasminoides Ellis (Rubiaceae). Their structures were elucidated by spectral and chemical methods.     

Concise,Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes

A practical synthesis of (−)‐englerin A was accomplished in 17 steps and 11 % global yield from commercially available achiral precursors. The key step consists of a platinum‐catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans‐fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99 % ee) stems from an asymmetric ruthenium‐catalyzed transfer hydrogenation of a readily assembled diene–ynone. The synthesis also features a highly stereoselective oxygenation, and a late‐stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.     

Four New Germine Esters from Veratrum dahuricum

Four new alkaloids, compounds 1 – 4 , based on the germine (=4,9‐epoxycevane‐3,4,7,14,15,16,20‐heptol; 5 ) framework, were isolated from the rhizomes of V. dahuricum, together with germine proper. The X‐ray crystal structure of germine ( 5 ) was solved, and all compounds were characterized by circular dichroism, 1D‐ and 2D‐NMR (¹H,¹H‐COSY, DEPT, HSQC, HMBC), as well as HR‐MS analyses.     

Synthesis,properties, and field effect transistor characteristics of new thiophene‐[1,2,5]thiadiazolo[3,4‐g]quinoxaline‐thiophene‐based conjugated polymers

Four new conjugated copolymers based on the moiety of bis(4‐hexylthiophen‐2‐yl)‐6,7‐diheptyl‐[1,2,5]thiadiazolo[3,4‐g]quinoxaline (BTHTQ) were synthesized and characterized, including poly(6,7‐diheptyl‐4,9‐bis(4‐hexylthiophen‐2‐yl)‐[1,2,5]thiadiazolo[3,4‐g]quinoxaline) (PBTHTQ), poly‐(6,7‐diheptyl‐4,9‐bis(4‐hexylthiophen‐2‐yl)‐[1,2,5]thiadiazolo‐[3,4‐g]quinoxaline‐alt‐2,5‐thiophene) (PTTHTQ), poly(6,7‐diheptyl‐4,9‐bis(4‐hexylthiophen‐2‐yl) [1,2,5]‐thiadiazolo‐[3,4‐g]quinoxaline‐alt‐9,9‐dioctyl‐2,7‐fluore‐ne) (PFBTHTQ), and poly(6,7‐diheptyl‐4,9‐bis(4‐hexylthiophen‐2‐yl)‐[1,2,5]thiadiazolo[3,4‐g]quinoxaline‐alt‐1,4‐bis(decyloxy)phenylene) (PPBTHTQ). The λ_max of PBTHTQ, PTTHTQ, PFBTHTQ, and PPBTHTP thin films was shown at 780, 876, 734, and 710 nm, respectively, with the corresponding optical band gaps (E) of 1.31, 1.05, 1.40, and 1.43 eV. The relatively small band gaps of the synthesized polymers suggested the significance of intramolecular charge transfer between the donor and TQ moiety. The estimated hole mobilities of PBTHTQ, PTTHTQ, and PFBTHTQ‐based field effect transistor devices using CHCl₃ solvent were 8.5 × 10^?5, 8.5 × 10^?4, and 2.8 × 10^?5 cm² V^?1 s^?1, respectively, but significantly enhanced to 1.6 × 10^?4, 3.8 × 10^?3, and 1.5 × 10^?4 cm² V^?1 s^?1 using high boiling point solvent of chlorobenzene (CB). The higher hole mobility of PTTHTQ than the other two copolymers was attributed from its smaller band gap or ordered morphology [wormlike (chloroform) or needle‐like (CB)]. The characteristics of small band gap and high mobility suggest the potential applications of the BTHTQ‐based conjugated copolymers in electronic and optoelectronic devices. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6305–6316, 2008     

Concise,Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes

A practical synthesis of (?)‐englerin A was accomplished in 17 steps and 11 % global yield from commercially available achiral precursors. The key step consists of a platinum‐catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans‐fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99 % ee) stems from an asymmetric ruthenium‐catalyzed transfer hydrogenation of a readily assembled diene–ynone. The synthesis also features a highly stereoselective oxygenation, and a late‐stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.     

A simple synthesis of 4‐chloro‐5‐hydroxy‐1H‐benzo[g]indoles

The reaction of methyl 2‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)propenoate ( 2a ) with primary amines gave 4‐chloro‐5‐hydroxy‐3‐methoxycarbonyl‐1H‐benzo[g]indoles 5a‐f as major compounds and 3‐methoxycarbonyl‐4,9‐dioxo‐2,3,4,9‐tetrahydro‐1H‐benzo[f]indoles 6a‐d as minor ones. Whereas the reaction of 3‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐3‐buten‐2‐one ( 2b ) with primary amines afforded the corresponding 1H‐benzo[g]indoles 5g‐i as major products and 3‐acetyl‐4,9‐dihydro‐4,9‐dioxo‐1H‐benzo[f]indoles 7g, h as minor products.     

A Rapid Sample Preparation Procedure Using MonoSpin CBA and Amide Columns for Tetrodotoxin Detection in Serum and Urine Using LC–MS/MS Analysis

Clinical diagnosis of tetrodotoxin (TTX) poisoning can be difficult because of the lack of characteristic morphological findings and a screening test, such as an immunoassay. Here, we present a fully validated method for the analysis of TTX in serum and urine. In this method, serum and urine samples were extracted using MonoSpin CBA or amide columns, followed by LC–MS/MS analysis. The TTX was eluted from the column by 0.1 mL of 10 % acetic acid solution, and was directly injected into LC–MS/MS. An Agilent 1200 HPLC system equipped with a HILIC separation column (Zorbax HILIC Plus 2.1 × 100 mm, 3.5 μm) was used for isocratic elution, with a mobile phase of 10 mM ammonium formate with formic acid (95:5, v/v), along with 5 mM trifluoroacetic acid and 2 % acetonitrile. TTX was detected with an Agilent 6410 mass spectrometer utilizing positive electrospray ionization and multiple reaction monitoring. Limits of quantification for serum and urine were established to be 1 and 0.5 ng mL^?1, respectively. Limits of detection for serum and urine were 0.5 and 0.25 ng mL^?1, respectively. Intra-day and inter-day precision varied from 1.5 to 8.5 %. The recovery was >86.5 % for both matrices. In this method, the sample preparation process prior to injection into the LC–MS/MS takes approximately 10–15 min, which reduces the extraction time to one-tenth of that of previous methods. The application of this method was further verified by analysis of biological materials from a patient suffering from puffer fish poisoning.     

New 9,10‐Secosteroids from Biotransformations of Hyodeoxycholic Acid with Rhodococcus spp.

The biotransformations of hyodeoxycholic acid with various Rhodococcus spp. are reported. Some strains (i.e., Rhodococcus zopfii, Rhodococcus ruber, and Rhodococcus aetherivorans) are able to partially degrade the side chain at C(17) to afford 6α‐hydroxy‐3‐oxo‐23,24‐dinor‐5β‐cholan‐22‐oic acid ( 2 ; 23%) and 6α‐hydroxy‐3‐oxo‐23,24‐dinorchol‐1,4‐dien‐22‐oic acid ( 3 ; 23–30%), together with two new 9,10‐secosteroids 4 and 5 (10–45%), still bearing the partial side chain at C(17) and adopting an intramolecular hemiacetal form. In addition, the 9,10‐secosteroid 5 showed an unprecedented C(4)‐hydroxylation. The new secosteroids were fully characterized by MS, IR, NMR, and 2D‐NMR analyses.